Coughing is a reflex action where the air is rapidly expelled from the lungs to clear excessive secretions, fluids, or foreign material from the airway. Therefore, cough is an important respiratory defense mechanism. However, coughing may also be a symptom of an underlying disease.
Apart from the discomfort of coughing itself, excessive coughing can cause multisystem problems. For example, it may lead to anxiety, fatigue, insomnia, muscle pain (myalgia), hoarseness (dysphonia), perspiring, and urinary incontinence (1).
Other difficulties, including heightened self-consciousness and changes in lifestyle, are also common consequences of chronic cough (2).
Cough is a common medical complaint. It is estimated to be responsible for approximately 30 million clinicians visits annually in the United States (3)
Most coughs clear up by themselves within three weeks. Such coughs are usually caused by an acute respiratory infection.
Cough is often classified based upon its duration. An acute cough exists for less than three weeks. Cough that has been present for more than three weeks is either subacute (3-8 weeks) or chronic (more than eight weeks)(4).
Several definitions are used when describing cough (5):
Acute cough: Sudden onset and lasts up to 3 weeks
Subacute cough: Lasts between 3-8 weeks
Chronic cough: Lasts for more than 8 weeks
Productive cough: Cough that brings up phlegm or mucus.
Dry cough: Cough that does not bring up phlegm or mucus
Nocturnal cough: Cough that only happens at night
Hemoptysis: Coughing blood
Acute cough exists for less than three weeks.
Because acute cough has a different range of causes in adults than it does in children, adults should be assessed and treated differently. The American College of Chest Physicians’ recommends that patients with acute cough be divided into children (younger than 15 years of age) and adults (15 years of age or older) (6).
The overwhelming majority of acute coughs are infectious in origin. These are commonly divided into upper and lower respiratory tract infections.
1. Common Cold
The common cold is the most frequent cause of acute cough. It is caused by a viral infection of the nose and throat and thus classified as an upper respiratory tract infection.
Other symptoms associated with the common cold are a sore throat, runny or stuffy nose, sneezing, low-grade fever, and body aches.
A cold virus enters the body through the upper respiratory tract (mouth, eyes or nose). The virus usually spreads by droplets in the air when someone with common cold coughs, sneezes or talks. It can also spread by hand-to-hand contact with someone who has a cold or through contaminated objects such as toys or telephones.
Children younger than six years are at highest risk of colds. Healthy adults can be expected to have two or three colds annually (7).
Most people recover from a common cold in 7-10 days. However, symptoms often last longer in smokers
2. Influenza (“the flu”)
Influenza, commonly called the flu, is a viral infection involving the respiratory system. The nose, throat, and lungs are often affected.
Fever, sore throat, headache, nasal congestion, aching muscles, a persistent dry cough, and fatigue are common influenza symptoms
Initially, the flu may seem like a common cold with sneezing, a runny nose, and sore throat. Whereas colds usually develop slowly, influenza tends to come on suddenly. Although a cold can be a nuisance, people typically feel much worse with the flu (8)
Influenza is highly contagious. The viruses travel in droplets spread by coughing and sneezing. These may be inhaled directly or spread by contaminated objects such as towels or telephones.
Usually, influenza resolves on its own. However, the complications of influenza may sometimes become severe and even deadly. This is most likely to occur in young children, old adults, pregnant women, patients with chronic illnesses, and people with a weakened immune system.
Pneumonia is the most severe complication.
The best defense against influenza is annual vaccination.
3. Acute Bronchitis
Acute bronchitis, also known as a chest cold, is a lower respiratory tract infection caused by an inflammation of the bronchial tree.
The bronchial tree consists of tubes that carry air into the lungs. When these tubes get infected, they swell, and mucus (thick fluid) forms inside them (9).
Acute bronchitis is a lower respiratory tract infection caused by an inflammation of the bronchial tree (the tubes that carry air into the lungs).
Acute bronchitis lasts for at least five days. It is typically self-limited, resolving within one to three week (10).
Cough is the most common symptom of acute bronchitis. It may be with or without sputum production.
Other symptoms include a sore throat, wheezing, shortness of breath, fever, chest discomfort, chills, and body aches.
Acute bronchitis is most often caused by a viral infection. These may even be the same viruses that cause the common cold.
Acute bronchitis may sometimes be caused by bacterial and fungal infections (9).
Exposure to irritants, such as smoke, dust, or fumes, also can cause acute bronchitis.
Acute bronchitis is usually a presumptive diagnosis, based on history and examination, when the patient presents with an acute, and typically productive, cough of less than three weeks’ duration.
Fever is not common in people with acute bronchitis. However, having a fever can be a sign of another condition, such as the flu or pneumonia (11).
Treatment is focused on patient education and supportive care. Antibiotics are not needed for the vast majority of patients. Antibiotics are greatly overused for this condition (8).
One of the reasons antibiotics are described is that many doctors are worried that they might miss a case of acute community-acquired pneumonia, which still has a relatively high mortality, especially among the elderly (12).
Pneumonia is an inflammation caused by an infection of the air sacs in the lungs.
The infection may be caused by bacteria, viruses, and fungi.
Community-acquired pneumonia is the most common type of pneumonia. It occurs outside of hospitals.
Pneumonia may be a complication of another condition, such as influenza.
Pneumonia is more likely to occur in patients with underlying chronic diseases such as chronic obstructive pulmonary disease (COPD), asthma or heart failure.
Patients with pneumonia often have a fever and a productive cough. Other symptoms include chills, chest pain, and difficulty breathing.
Hospital-acquired pneumonia occurs during a hospital stay, usually when patients are being treated for another illness. It may be serious because these patients are often more vulnerable and the bacteria responsible may be resistant to antibiotics.
5. Whooping Cough (Pertussis)
Whooping cough is a highly contagious respiratory infection affecting the airways and lungs.
It is caused by a type of bacteria called Bordetella pertussis which spreads in the droplets of the coughs or sneezes of someone with the infection (13).
The first symptoms are usually similar to those of a common cold, such as a sore throat and a runny nose. About a week later, a severe hacking cough often develops, sometimes followed by a high-pitched intake of breath that sounds like “whoop.”
However, many patients don’t develop the classic whoop.
The coughing bouts usually last a few minutes at a time. The coughing usually brings up thick mucus, sometimes followed by vomiting.
Today, whooping cough primarily affects children too young to have completed the full course of vaccinations and teenagers and adults whose immunity has faded (14). Vaccination secures immunity for no more than a few years.
Adult patients often present an atypical mild disease course with a nonspecific dry cough.
6. Worsening of Chronic Obstructive Pulmonary Disease (COPD)
While chronic obstructive pulmonary disease (COPD) is a mainly chronic disease, a substantial number of patients suffer from exacerbations characterized by worsening or “flare up” of symptoms.
In many cases, the worsening is from an infection of the airways or lungs or from inhaling irritating substances from the environment. However, in many cases, the cause is unknown.
Typical symptoms include more breathlessness than usual, a change in sputum (color or amount), increased cough, more tiredness (fatigue), trouble sleeping and in some cases, a fever (15).
7. Pulmonary Embolism (PE)
Pulmonary embolism is a blockage in one or both of the pulmonary arteries within the lungs.
It is caused by blood clots that travel from the lower extremities, through the right heart chambers, and lodge in the lungs. Pulmonary embolism can be life-threatening (16).
In most cases, a blood clot in the deep veins of the leg, called deep vein thrombosis (DVT), is the underlying cause of pulmonary embolism. Painful swelling of one leg, ankle or feet should raise the suspicion of DVT (17).
The most common symptoms of pulmonary embolism include shortness of breath, cough, and sometimes chest pain that gets worse when breathing (pleuritic pain). Signs of DVT in one or both legs may be found.
8. Acute Inhalation Injury
Inhaled substances may cause injury to the airways and lead to acute cough. This may occur at various places including the home and workplace (18).
Examples of common chemical irritants are ammonia, hydrogen chloride, hydrogen sulfide, hydrogen fluoride, sulfur dioxide, oxides of nitrogen, and chlorine.
Smoke inhalation from fires is common among firefighters and non-occupational victims.
Individuals who are accidentally exposed to toxic gases usually recover completely. However, sometimes acute life-threatening or chronic severe complications may develop (18).
Subacute and Chronic Cough
A cough that has been present for more than three weeks is either subacute (3-8 weeks) or chronic (more than 8 weeks)(4).
9. Postinfectious Cough
Patients may complain of a persistent cough following acute respiratory infections such as the common cold or acute bronchitis.
If a cough lasts for more than three weeks, it is no longer considered to be an acute cough. Instead, it falls into the category of a subacute cough.
One study found that postinfectious cough was the most common cause of subacute cough. The study also found that such cough frequently resolves without specific therapy (19).
10. Upper Airway Cough Syndrome (UACS)
The American College of Chest Physicians defines upper airway cough syndrome (UACS) as a syndrome characterized by chronic cough (i.e., present for ≥8 weeks) related to upper airway abnormalities (20).
UACS is typically associated with postnasal drip and the presence of mucus in the throat (21).
Postnasal drip occurs when excessive mucus is produced by the mucosal cells that line the nasal cavity. The excess mucus accumulates in the throat or at the back of the nose (nasopharynx) (22).
Symptoms of postnasal drip include frequent nasal discharge and a sensation of liquid dripping in the back of the throat (4). This is often followed by frequent throat clearing. However, many patients with postnasal drip don’t experience these symptoms. In these cases, chronic cough may be the sole complaint.
Several remedies for UACS may be helpful. A humidifier or steam inhalation may be useful. Keeping well hydrated may help keep the mucus thinner. In some cases, sleeping on propped up pillows may prevent the mucus from collecting at the back of the throat (23).
Nasal irrigation, usually available over the counter, may help and so can oral decongestants such as pseudoephedrine (as in Sudafed) or phenylephrine (as in Sudafed PE or Neo-Synephrine). Guaifenesin (as in Mucinex) is a medication that can thin the mucus (24).
Antihistamines (diphenhydramine, chlorpheniramine, loratadine, desloratadine, fexofenadine, cetirizine levocetirizine) and nasal decongestants may be helpful. However, nasal decongestants should only be used for a day or two as more extended treatment may make the situation worse.
Asthma is the second leading cause of chronic cough in adults, and the most common cause in children (25).
Asthma is a condition in which the airways narrow and swell and produce extra mucus. This can cause shortness of breath, wheezing, tightness in the chest, and a nonproductive cough (26).
Some patients with asthma have infrequent attacks or have symptoms under certain conditions, such as when exercising, while others have more frequent or chronic symptoms.
Allergy-induced asthma is triggered by airborne substances such as pollen, spores, dust mites, and pet dander. Other allergic symptoms such as watery eyes and runny nose are common.
Exercise-induced asthma is typically provoked by exercise and often gets worse when the air is cold and dry.
Occupational asthma is usually triggered by workplace irritants such as chemical fumes or dust.
12. Gastroesophageal Reflux
Gastroesophageal reflux is believed to be the second or third most common cause of chronic cough(4).
Gastroesophageal reflux disease (GERD) is a chronic digestive disease that occurs when stomach acid or, occasionally, stomach content, flows back (reflux) into the esophagus. The reflux irritates and may damage the lining of the esophagus causing the disease (27).
Most healthy people experience acid reflux and heartburn once in a while. However, when these symptoms occur at least twice each week or interfere with daily life, GERD should be suspected.
However, many patients with GERD don’t experience acid reflux or heartburn. In these cases, cough may be the only symptom.
Most people can manage the symptoms of GERD with lifestyle changes and over-the-counter medications. But some patients may need prescription drugs, or even surgery, to reduce symptoms.
Proton pump inhibitors such as Nexium, Protonix, Prevacid, Aciphex, or Prilosec are particularly helpful.
13. Laryngopharyngeal Reflux (LPR)
Laryngopharyngeal reflux (LPR) is a condition that develops when stomach acid travels up into the throat. Although some patients also experience “heartburn” or “indigestion,” many do not have these complaints.
Typical symptoms include chronic cough, hoarseness (dysphonia), frequent throat clearing, sore throat and difficulty swallowing (28).
Most of the time, LPR is well controlled with lifestyle changes and medications (proton pump inhibitors).
14. Obstructive Sleep Apnea (OSA)
Obstructive sleep apnea (OSA) is a relatively common sleep disorder with several potentially serious consequences. It causes breathing to stop and then start again intermittently during sleep (29).
OSA occurs when the throat muscles intermittently relax and block the airways during sleep causing a repetitive obstruction of the upper airway during sleep.
OSA may seriously affect the quality of life and is strongly associated with the risk of diabetes, high blood pressure, liver disorders, and cardiovascular disease.
Recent reports have shown a resolution of chronic cough in many patients following treatment of concomitantly diagnosed OSA (30).
However many patients with OSA also suffer from gastroesophageal reflux disease (GERD), upper airway cough syndrome (UACS), and cough related asthma. Whether cough in patients with OSA is caused by these disorders or directly related to the OSA itself is unknown.
15. Chronic Bronchitis
Chronic obstructive pulmonary disease, or COPD, refers to a group of conditions that cause airflow blockage leading to shortness of breath, cough, mucus (sputum) production and wheezing. It includes emphysema, chronic bronchitis, and in some cases asthma (26).
Tobacco smoke is the leading cause of the development and progression of COPD (31).
COPD was the third leading cause of death in the United States in 2014 (4).
Emphysema and chronic bronchitis are the two most common conditions that contribute to COPD.
Chronic bronchitis is defined as a productive cough that lasts at least three months, with recurring bouts occurring for at least two consecutive years. It is caused by an inflammation of the lining of the bronchial tubes leading to shortness of breath, a daily cough and mucus production. Almost all patients are smokers.
Bronchiectasis is a condition in which damage to the airways (bronchi) causes them to widen and become flabby and scarred (32). It usually results from repeated or persistent inflammation of the airways.
In bronchiectasis, the airways slowly lose their ability to clear out mucus. Consequently, mucus builds up and creates an environment in which bacteria can grow, leading to repeated, serious lung infections.
Cough is a major symptom of bronchiectasis.
17. Interstitial Lung Disease (ILD)
The term interstitial lung disease (ILD) refers to a broad category of lung diseases rather than a distinct disease entity. Hence, it includes a variety of illnesses with different underlying causes. These disorders are grouped together because of similarities in their clinical presentations, radiographic appearance, and physiologic features (33).
The abnormalities that characterize ILD involve the lung interstitium (the area between the capillaries and the alveolar space) to a greater extent than the alveolar spaces or airways. The interstitium supports the delicate relationship between the alveoli and capillaries, allowing an efficient gas exchange (26)
The lungs may be initially injured by external exposure (e.g., asbestos, drugs, moldy hay), an underlying autoimmune disease (e.g., rheumatoid arthritis) or some unknown agent (idiopathic pulmonary fibrosis).
Lung function may become severely reduced in ILD. Gas exchange is impaired, and the work of breathing is increased because of decreased lung compliance.
Shortness of breath and a nonproductive cough are the most common symptoms.
Therapy depends on the underlying disease and may consist of immunosuppressive drugs and avoidance of disease-inducing exposures.
Smoking is a major risk factor for lung cancer
18. Lung Cancer
Evidence suggests that less than 2 percent of chronic cough is caused by lung cancer (34).
Other symptoms associated with lung cancer include chest pain, breathlessness and coughing up blood (hemoptysis)(26).
Smoking is the most significant risk factor for lung cancer.
19. Heart Failure
Patients with heart failure may experience a persistent cough or wheeze with white or pink blood-tinged phlegm (35).
Heart failure occurs when the heart muscle is weakened and cannot pump enough blood to meet the body’s needs for blood and oxygen. In some cases, the pumping capacity of the heart muscle is preserved, but the left ventricle is stiff with decreased compliance and impaired relaxation, leading to increased filling pressure in the left ventricle (26).
Heart failure is caused by an underlying heart disease that has caused damage to the heart muscle and/or increased stiffness of the heart muscle. Coronary heart disease, hypertension, valvular disorders, and dilated cardiomyopathy are the most common causes of heart failure.
Heart failure frequently presents with shortness of breath on exertion, fatigue,..
In the early fall of 1975, two mothers from Old Lyme, Connecticut, desperately sought medical help because of a mysterious outbreak of a strange, unexplainable disease. Both children and adults were affected, and arthritis appeared to be the most prominent symptom.
It was soon discovered that many patients also reported a skin lesion with an expanding bulls-eye pattern a few weeks preceding the onset of arthritis (1).
The lesion matched the description of or erythema migrans, a skin lesion previously reported in Europe and thought to be a result of an infectious agent. However, this was the first time erythema migrans had been associated with arthritis (2).
In December 1975, a surveillance study was carried out in Lyme and surrounding towns on the eastern bank of the Connecticut River. The study was led by Allan C. Steere, MD, and Stephen E. Malawista, MD, from the Rheumatology section of the Yale School of Medicine.
In 1976, Steere and Malawista suggested that Lyme arthritis was a tick-borne disease. They published evidence showing the that the incidence of the disorder was 30 times greater on the east side of the river, where Lyme is located than it was on the west side, similar to the difference in deer and deer tick distribution in the area (3).
Scientists later confirmed that ticks indeed are the transmission vector of the infectious agent in Lyme disease.
The risk of Lyme disease is year round, but the highest risk window is late spring into early summer.
Over 300,000 new cases of Lyme disease are estimated to occur every year in the United States (4). Today, Lyme disease is the most common tick-borne disease in the United States, Canada, and Europe.
Fortunately, Lyme disease is rarely life-threatening.
1. What Is the Cause of Lyme Disease?
Lyme disease is caused by a few different species of the spirochete Borrelia.
Spirochetes are long and slender cork-screw-like bacteria, usually only a fraction of a micron in diameter but 5 to 250 microns long. They are tightly coiled and look like small springs or telephone cords (5).
In North America, Lyme disease is caused primarily by Borrelia Burgdorferi (6). In Europe and Asia, infections caused by Borrelia afzelii, and Borrelia garinii are more common.
Spirochetes are cork-screw-like bacteria that look like miniature springs or telephone cords.
In the northeastern United States, rodents such as the white-footed mouse are the primary reservoir of the Borrelia species.
The spirochetal infection is transmitted by the bite of infected ticks
The risk of exposure to ticks is highest in the woods and the edge area between lawns and woods. Ticks may also be carried by animals and pets onto parks and gardens and into houses. Campers, hikers, and outdoor workers may be exposed in wooded, brushy, and grassy places.
2. How Do Ticks Transmit Lyme Disease?
The spirochetal infection causing Lyme disease is transmitted by the bite of infected ticks of the Ixodes ricinus complex.
There is no evidence that Lyme disease is transmitted from person-to-person through touching, kissing, having sex or sharing silverware or glasses with a person with Lyme disease.
The three tick species that commonly bite people in the eastern United States include the blacklegged tick, the Lone Star tick, and the American dog tick. The blacklegged tick is the only one that transmits Lyme disease in the United States (7).
The blacklegged tick (or deer tick, Ixodes scapularis) spreads the disease in the northeastern, mid-Atlantic, and north-central United States, and the western blacklegged tick (Ixodes pacificus) spreads the disease on the Pacific Coast.
It is believed that ticks need to be attached for 36 to 48 hours before they can transmit Lyme disease bacteria.
Ticks obtain blood by inserting their mouth parts into the skin of a person or animal. As they feed, their bodies slowly enlarge.
Most humans are infected through the bites of immature ticks called nymphs. Nymphs are tiny and often difficult to see. Adult ticks also transmit Lyme disease bacteria, but they are much larger and are more likely to be discovered before they have had time to transfer the bacteria (8).
Ticks obtain blood by inserting their mouth parts into the skin of a person or animal. Ixodes ticks are slow feeders, and one meal can take several days. As they feed, their bodies slowly enlarge.
3. In What Areas Is Lyme Disease Most Common?
For Lyme disease to exist in an area, three environmental elements must be present (8):
animals that are infected with Lyme disease bacteria
ticks that can transmit the bacteria, and
animal hosts (such as mice and deer) that can provide food for the ticks in their various life stages
Lyme Disease is present in North America, Europe, and Asia.
Travelers involved in outdoor activities in forested areas are at risk, including campers, hikers, and hunters. Brushing against vegetation or walking in city parks known to have infected ticks can also put a person at risk.
Risk of Lyme Disease increases during the warmer months when ticks are most active. However, ticks can be found year-round in areas where temperatures are above freezing.
Lyme disease is distributed over a wide geographic area in northern temperate regions of the world.
In the United States, most infections occur in the following areas (8):
Northeast, from Virginia to Maine
North-central states, mostly in Wisconsin and Minnesota
West Coast, mainly northern California
4. What Are the Symptoms of Lyme Disease?
The signs and symptoms of Lyme disease are often divided into three clinical stages. However, the clinical features may overlap and some patients present at a later stage with no history of prior signs of the disease (7).
The first stage is characterized by the occurrence of the red, circular, bulls-eye rash called erythema migrans.
The second stage sometimes called early disseminated disease, is characterized by multiple erythema migrans lesions that occur days to weeks following the tick bite. During this period neurological symptoms may occur, including numbness, pain, nerve paralysis, and meningitis (fever, stiff neck, and severe headache). Although rare, some patients experience cardiac involvement including an irregular heartbeat.
The most common clinical manifestations include fatigue, anorexia, headache, neck stiffness, muscle aches (myalgia), joint pain (arthralgias), enlarged lymph nodes, and fever (6).
It is important to acknowledge that different people exhibit different signs and symptoms of Lyme disease. Some patients never develop erythema migrans, some only develop arthritis, and some patients only have neurological symptoms.
General symptoms such as fever, muscle aches, and fatigue can be mistaken for viral infections such as influenza. Joint pain can be mistaken for other types of arthritis, and neurologic signs may be similar to those experienced by patients with multiple sclerosis or peripheral neuropathy of another origin.
The third stage, late Lyme disease is characterized by arthritis involving one or more large joints, especially the knee. Late Lyme disease may occur months to few years following the tick bite and is not always preceded by a history of early localized or disseminated disease.
Neuropsychiatric manifestations may be present during late Lyme Disease. These may include cognitive disturbances and polyneuropathy. The latter is characterized by pain and paresthesias (9).
In Europe, some patients develop a chronic skin condition called acrodermatitis chronica atrophicans (10). It may appear months to years after the initial infection and is mainly due to Borrelia afzelli. The condition is not known to occur in the United States.
5. What Is Erythema Migrans?
The first stage of Lyme Disease, early localized disease, is characterized by a skin lesion called erythema migrans.
Erythema migrans is a red circular rash that often appears at the site of the tick bite. It usually occurs within a month following the bite, most often within the first 3 to 14 days.
Erythema migrans occurs in 80% of patients with Lyme disease (11).
The rash typically expands slowly over the course of days or weeks. Sometimes many rashes appear, varying in shapes and sizes. They are often found on the thighs, groin, trunk, and armpits.
The center of the rash may clear as it enlarges, resulting in a “bulls-eye” appearance. Although the central clearing is classic for erythema migrans, it is usually not present during the first days of the rash.
Erythema migrans is not particularly painful but may occasionally burn or itch and is usually hot to the touch.
Not all rashes that occur at the site of a tick bite are due to Lyme disease. An allergic reaction to tick saliva can also occur and be confused with the rash of Lyme disease. It most often appears within hours to a few days after the tick bite, usually, do not expand, and disappear within a few days.
The classic bulls-eye rash associated with Lyme disease is called erythema migrans.
6. What Are Post-Lyme Disease Syndrome and Post-Treatment Lyme Disease Syndrome (PTLDS)?
The terms pos”post-Lyme disease syndrome” and post-treatment Lyme Disease Syndrome (PTLDS) are sometimes used to describe general symptoms that may be present for long periods after Lyme disease has been treated.
Examples of such symptoms are headache, fatigue, joint pain (arthralgias), musculoskeletal pain, and cognitive difficulties. In most cases, these symptoms disappear gradually in six to twelve months.
Between 5-15 percent of patients treated for Lyme disease may develop PTLDS. The cause of the disorder is unclear but is not believed to be due to persistent or ongoing infection following treatment.
7. What Is Neuroborreliosis?
The term Neuroborreliosis or Lyme neuroborreliosis (LNB) is sometimes used to describe the neurologic manifestations of Lyme disease (12).
Neuroborreliosis may occur during the early and late stages of Lyme disease.
The nervous system is involved in 10% to 15% of cases early Lyme disease (13)
Early neuroborreliosis may present with facial palsy (inability to control the facial muscles on the affected side of the face), meningitis and painful radiculoneuritis (inflammation of one or more roots of the spinal nerves). It usually occurs within about six to twelve weeks following the infection.
The symptoms of acute neuroborreliosis usually disappear following antibiotic treatment.
Late/chronic Lyme neuroborreliosis is characterized by various neuropsychiatric manifestations (14).
The clinical symptoms include seizures, speech difficulties, ataxia (lack of control of voluntary muscle movements), chronic spastic para- tetra- and hemiparesis, mood disorders, psychosis, visual and auditory hallucinations, paranoia, anorexia nervosa, and obsessive-compulsive disorder (15).
8. What Diseases May Resemble Lyme Disease?
Known as “The Great Imitator,” Lyme disease may mimic many other conditions. This may lead to several difficulties in diagnosis.
Muscle aches, fever, and headache are common symptoms of flu. These are also experienced by many patients with Lyme disease.
Arthritis, a common symptom of Lyme Disease, may have many other causes. It may be mistaken for rheumatoid arthritis, gout, osteoarthritis or degenerative arthritis.
Some patients with Lyme disease suffer from chronic fatigue. This may be mistaken for chronic fatigue syndrome or fibromyalgia.
The neuropsychiatric symptoms of Lyme disease may mimic Parkinson’s disease, multiple sclerosis, Alzheimer’s and depression.
9. How Is Lyme Disease Diagnosed?
The diagnosis of Lyme disease should take into account the patients history and exposure to ticks in areas where Lyme disease is known to occur. Hence, detailed travel and activity history is essential.
The diagnosis of early Lyme disease is made on clinical grounds, primarily based on the presence of erythema migrans. Lab tests are unlikely to support the diagnosis at this stage because the immune system will not have had enough time to produce antibodies.
During early disseminated disease and late Lyme disease, lab testing plays a vital role. For serologic testing, a two-tier conditional strategy is recommended (16):
Enzyme-linked immunosorbent assay (ELISA) test is used most often to detect Lyme disease and detects antibodies to Borrelia burgdorferi. A different type of enzyme immunoassay (immunofluorescent assay or IFA) may be substituted for the ELISA test. However, both these tests can sometimes provide false positive results and are therefore not used as the sole base for diagnosis.
If the ELISA test is positive, the Western blot test is usually done to confirm the diagnosis.
A negative Western blot test supersedes the result of a positive ELISA or IFA, and testing should be considered negative. A positive Western blot test is considered evidence of an encounter with Borrelia burgdorferi (16).
10. How Is Lyme Disease Treated?
Several antibiotics are useful for treating Lyme disease. These are usually given by mouth but may be given intravenously in more severe cases.
Patients treated with antibiotics in the early stages of the infection usually recover rapidly and completely.
Most patients who are treated in later stages of the disease also respond well to antibiotics.
A few patients may have persistent or recurrent symptoms and may require an additional course of antibiotic treatment. Longer courses of antibiotics have not been shown to be beneficial in patients who have been previously treated and have chronic symptoms.
Antibiotics commonly used for oral treatment include doxycycline, amoxicillin, or cefuroxime axetil. People with specific neurological or cardiac forms of illness may require intravenous treatment with antibiotics such as ceftriaxone or penicillin (17).
11. How Is Lyme Disease During Pregnancy Treated?
Untreated Lyme disease during pregnancy may lead to infection of the placenta and possible stillbirth. However, no severe effects on the fetus have been found in cases where the mother receives appropriate antibiotic treatment for her Lyme disease (18).
In general, treatment for pregnant women with Lyme disease is similar to that of non-pregnant adults, although certain antibiotics, such as doxycycline, are not used because they can affect fetal development.
Additionally, there are no reports of Lyme disease transmission from breast milk.
12. How Can Tick Bites Be Prevented?
It is possible to decrease the chances of being bitten by a tick with a few precautions. Avoiding tick-infested areas is the first rule. This is especially important in May, June, and July.
If you live in a risk area, keeping your lawn well manicured and adding a deer fence may be helpful. Because ticks get Lyme disease from mice, eliminating the mouse habitats around your yard is important. This includes removing wood piles and rock piles where the mice tend to live and breed (4).
During outdoor activity, it is important to avoid wooded, overgrown areas and stay out of tall grass and the uncleared regions of the forest. Staying on marked trails is recommended when hiking.
Wearing protective clothing is recommended. That includes long sleeves, long pants and avoid going barefoot or wearing open shoes.
Insect repellant containing DEET, picaridin, IR3535, oil of lemon eucalyptus, para-menthane-diol, or 2-undecanone may be used on the body and Permethrin on clothes. It is imperative always to follow the manufacturer’s instructions when applying these substances.
Permethrin should not be applied to your skin. It is a unique substance and does not need to be reapplied frequently because it stays bound to clothes for several months.
It is a good protective habit to shower immediately or within two hours of coming indoors.
Always check for ticks after being outdoors. Ticks are tiny and sometimes hard to see. By feeling for ticks, they may be found in hidden areas, such as behind your knee or in your armpit
13. How Should Attached Ticks Be Removed From the Skin?
Because ticks must usually be attached for at least a 24 hours before they can transmit the spirochetes causing Lyme disease, early removal reduces the risk of infection.
The quickest way to remove a tick is with tweezers. Grasp the tick between the head of the tick and the skin and to pull softly but securely away.
Sometimes, parts of the mouth of the tick will be left in the skin. However, these small mouthparts do not transmit Lyme disease and should be left alone. Just leave them in place. They will work their way out on their own.
Grasp the tick between the head of the tick and the skin and pull softly but securely away.
14. Is a Lyme Disease Vaccine Available?
LYMErix, a vaccine for Lyme disease, received licensing and approval from the U.S. Food and Drug Administration (FDA) in 1998, but the manufacturers (GlaxoSmithKline — then called SmithKline Beecham) stopped selling it in 2002, due to a lack of demand.
The vaccine was based on a specific part of B. burgdorferi called outer surface protein A (OspA). It was found to be between 49 and 68 percent effective in preventing Lyme disease after two injections, and 76 to 92 percent effective in preventing Lyme disease after three injections
In April 2002, GSK announced that even with the incidence of Lyme disease continuing to rise, sales for LYMErix declined from about 1.5 million doses in 1999 to a projected 10,000 doses in 2002. Although studies conducted by FDA failed to reveal that any reported adverse events were vaccine-associated, GSK discontinued manufacturing the vaccine (19). Since then, a new vaccine has yet to appear on the market.
15. Do Ticks Transmit Other Diseases than Lyme Disease?
Lyme disease is the most common tickborne disease in the United States, Canada, and Europe. However, ticks may carry several other diseases than Lyme disease.
Examples of tickborne diseases in the United States are (20):
Borrelia miyamotoi Disease
Colorado Tick Fever
Heartland and Bourbon Virus Diseases
Powassan Virus Disease
Rocky Mountain Spotted Fever
Rickettsia parkeri Rickettsiosis
Tickborne Relapsing Fever
Examples of tickborne diseases found in other countries are (21)
African Tick Bite Fever (ATBF, found in Sub-Saharan Africa, Caribbean (French West Indies), and Oceania)
Tickborne Encephalitis (TBE, endemic in focal areas of Europe and Asia, extending from eastern France to northern Japan and from northern Russia to Albania)
Mediterranean spotted fever (also known as boutonneuse fever (found in Europe (Mediterranean basin), Middle East, Indian subcontinent,
Crimean-Congo hemorrhagic fever /found in Asia, Africa, and Europe).
Omsk hemorrhagic fever (found in Southwestern Russia)
Kyasanur Forest disease (found in Southern India, Saudi Arabia (aka Alkhurma disease in Saudi
Migraine is characterized by recurrent attacks of headache. The pain is often described as throbbing, and there may be a pulsing sensation, usually on one side of the head. Migraines are commonly accompanied by nausea, vomiting, and sensitivity to light and sound (1).
The exact cause of migraines is unknown, but they’re believed to be the result of abnormal brain activity, partly caused by imbalances in brain chemicals including serotonin. These abnormalities may temporarily affect nerve signals and blood vessels in the brain.
Prodromal symptoms often occur one or two days before the headache (2). These include constipation or diarrhea, mood changes, appetite changes including food cravings, concentration difficulties, cold extremities, increased thirst, frequent urination and constant yawning.
Warning symptoms known as aura may occur before and sometimes together with the attack. Examples are visual disturbances and sensory abnormalities such as a tingling or touching sensation on one side of the face or in an arm or a leg (3). However, 75-80% of patients don’t experience an aura.
There are known environmental factors that we can come across every day that can “trigger” migraine headaches. These include foods and food additives, medications, emotional stress, menstruation, visual stimuli such as bright lights, fasting, wine, physical exertion, sleep disturbances, intake of highly caffeinated beverages and aspartame (4).
10 Everyday Things that May Trigger Migraines
Knowledge of the most common external triggers for migraine attacks is of crucial importance for individuals who suffer from migraine.
Certain foods and food ingredients may trigger migraine attacks. For instance, a very common ingredient in diet and low-calorie foods is the sugar substitute aspartame. This artificial sweetener can affect dopamine and serotonin levels in the brain, which can be a factor in migraine headaches (5).
Another common substance in food that may hasten the onset of a migraine is monosodium glutamate, best known as MSG (6). It’s often used to flavor Chinese food, but can also be found in soups and processed meats.
Nitrites are preservatives frequently found in sausage, beef jerky, hot dogs, deli meats and other meats. Nitrate-containing compounds have been identified as common headache triggers (7).
If you suffer from migraine, the next time you get invited to a wine and cheese party, you may want to RSVP no. Wine contains preservatives called sulfites, which can potentially induce migraines (8). Sulfites can also be found in processed foods, including dried fruits.
As for the cheese plate, aged cheeses have an amino acid called tyramine, which has been associated with migraines (9).
If you think you’ll skip the cheese in favor of the fruit that’s usually paired with it, well, think again. You may be opening yourself up to a migraine attack if you eat apples or pears, which contain tannins. This natural plant substance can also be found in tea, black walnuts, red wine, tea, chocolate, vanilla, raspberries, and many herbal products
Research shows that reducing tannin in the diet may reduce the risk of migraine attacks (10).
Finally, whatever you eat, handle it carefully, especially if you tend to eat leftovers for meals. The same tyramine that can be an issue in certain cheeses can multiply in foods, especially if it’s not properly refrigerated.
In addition to wine, there are other beverages that may cause trouble for you if you are a migraine sufferer. Alcohol is known to trigger a headache if too much is consumed—ask anyone who’s ever had a hangover—and studies suggest that alcohol and migraine symptoms are linked (11).
On the other hand, caffeine has a more mixed effect on migraines—depending on the person, caffeine can lead to a migraine or guard against one. If you note that you experience symptoms after a cup of coffee, you may want to cut back on your consumption (12).
So what can you drink? Water is always a safe, and a healthy choice. In fact, if you don’t drink enough water, you may experience dehydration, and that may lead to a migraine attack.
Identifying Your Migraine Triggers
It may not always be easy to determine what environmental factors are triggering migraines. In fact, migraine attacks may be linked to a number of different things. Furthermore, a potential trigger may not precipitate an attack every time.
Sometimes, trigger factors can influence an attack up to 48 hours before a headache occurs. Such trigger factors may easily be ignored.
One study showed that most patients showed at least one dietary trigger, fasting was the most frequent one, followed by alcohol and chocolate. Hormonal factors appeared in 53% with the pre-menstrual period being the most frequent. Physical activities triggered migraine in 13%, sexual activities in 2.5%, 64% reported emotional stress as a trigger, and 81% related some sleep problem as a trigger factor. Regarding environmental factors, smells were reported by 36.5%.
One of the best ways of identifying triggers is to keep a migraine diary. Such a diary should keep a record of daily activity such as when you get up and go to sleep, what you do during the day, what you eat and drink, the surroundings, the weather, the medication you take, your mood, and the menstrual cycle if you are a woman.
Registering the timing of the attacks is essential. For example, if you suffer at weekends, your headache may be triggered by caffeine withdrawal due to drinking fewer cups at home than at work. It may also be due to more wine or alcohol consumption on the weekends. Some people with migraine find that winding down at the weekend after a stressful week or too much sleep at the weekends can trigger an attack (13).
Reports of possible cabin air contamination onboard aircraft on commercial flights have become increasingly common in recent years. Such incidents are often described as fume events.
Most often, fume events describe abnormal odors, smoke, haze or fumes in the cabin which may arise from various internal or external sources in an aircraft.
More specifically, the term “fume event” is used to refer to a potentially toxic environment created by contaminated bleed air used to pressurize and ventilate aircraft cockpit and cabins.
However, bleed air contamination is not the only cause of fume events or medical symptoms among passengers and crew onboard commercial aircraft. Reduced oxygen levels, ozone, de-icing fluids, insecticides, fuel vapor, and fumes from ground service vehicles or other aircraft may also be responsible (1).
Hence, the term “air quality incident” is probably more appropriate than “fume event” or “bleed air contamination.”
Concerns have repeatedly been raised about the possible adverse health effects of exposure to contaminants in cabin air. Although known for decades, air quality incidents continue to represent potential safety hazards for passengers and crew on commercial flights.
Reports of suspected fume events often reach the news media.
In October 2016, British Airways flight BA286 from San Francisco to London was diverted to Vancouver after members of the crew became unwell, the airline said on Tuesday.
Michele Kropf, a spokeswoman for British Airways, said 25 crew members were taken to local hospitals as a precaution, but had now been discharged. There were 22 cabin crew and three pilots on board the plane.
But on Wednesday morning ABC News obtained a recording of the conversation between the pilot and Air Traffic Control.
“Can you say again the emergency for me please?” the controller asked.
The pilot replied: “Toxic fumes. Toxic gas-type fumes.”
BA did not comment on the cause of the problem (2).
Sometimes, crewmembers have reported a visible haze or smoke in the cabin/flight deck, or a smell often described as “dirty socks,” “chemicals,” “vomit,” or “burning oil.”
In 2017 an American Airlines Airbus A319-100, registration N829AW performing flight AA-1927 from Charlotte, NC to Raleigh/Durham,NC (USA), was enroute when a foul odour developed on board causing a number of passengers to suffer from nausea and headache.
The aircraft continued to Raleigh for a safe landing and taxied to the gate, where the passengers disembarked normally. A number of passengers received medical attention at the airport (3).
Not all odors detected within an aircraft cabin arise from oil contamination of the air supply. For example, they can originate from toilets and galley areas.
How often air quality incidents occur is difficult to determine. Furthermore, the nature of contaminants within the cabin air is usually unclear as commercial aircraft do not have air quality monitoring systems on board.
The immediate health effects of exposure to contaminated cabin cair have been relatively well documented. However, the causation, diagnosis, and treatment of long-term effects continue to be debated.
What Is Bleed Air?
For decades, aircraft have used engine bleed air for a variety of purposes, spanning everything from engine starting to cabin pressurization and anti-icing.
When air enters the flight engine, it goes through several compressors, increasing the air temperature and pressure before mixing it with fuel and igniting it.
A portion of the compressed air does not enter the combustion chamber but is redirected from the engine to various other parts of the aircraft. This so-called bleed air is very hot, between 200 to 250 degrees C, and very high in pressure, around 40 psi (4).
After leaving the engine and passing through the air-conditioning pack, where it is cooled, the bleed air is combined with recirculated cabin air before it enters the cabin.
Temperature controllers in the flight deck and cabin allow adjustment of the target temperature and thermostats provide feedback to the packs to demand an increase or decrease in the output temperature (5).
On most commercial aircraft, engine bleed air is used to provide appropriate cabin pressurization and air conditioning. In early commercial jet aircraft, passenger cabins were ventilated with 100% outside air. In more recent jet aircraft, approximately 50% of the ventilation air is outside air, and the remaining 50% is filtered recirculated cabin air.
With the introduction of the B787, Boeing has incorporated a new no-bleed systems architecture. Most of the functions formerly powered by bleed air have been replaced by electrically driven compressors.
Bleed Air Contamination
Bleed air is a heterogeneous mixture of constituents that may include gases, vapors, smoke, fumes, and mist, each of which is potentially associated with risk of adverse health effects following exposure (1).
Under certain failure conditions, toxicants such as pyrolyzed engine oils and hydraulic fluids may leak into the cabin air supply systems.
Several factors may contribute; oil seals that otherwise separate the “wet side” of the air compressor from the “dry side” can leak or fail and workers may overfill the oil/hydraulic fluid reservoirs or may spill oil/hydraulic fluid when filling the reservoir (6).
The airborne toxicants form a complex mixture, including 1-5% tricresylphosphates (TCPs) and N-phenyl-L-naphthylamine (PAN). If the air supply system temperature is high enough, engine oil and hydraulic fluid may also generate carbon monoxide (CO).
Tributyl phosphate (TBP), a constituent of hydraulic fluid may also be of health concern.
BLEED AIR explained - YouTube
Specific concerns have been raised regarding so-called tricresylphosphates (TCPs) in the cabin air environment and their perceived effects on health.
TCPs are added to most synthetic jet engine oils due to their anti-wear properties.
Although TCP additives are not the only toxic component of jet engine oils, they have repeatedly become a major source of debate.
Small amounts of TCPs have been found in cabin air under normal operating conditions on commercial flights (7).
Interestingly, TCP concentrations do not correlate with visible smoke/fume or odor detection (6).
Ten TCP molecules containing different combinations of the meta, ortho and para isomers, have been described. Jet engine oils contain a mixture of these molecules. These toxic mixtures can cause transitory and permanent damage to the nervous system when swallowed in sufficient quantity (8).
It is believed that the neurotoxicity of TCP is mainly due to its ortho isomers, such as tri-ortho-cresyl phosphate (TOCP). In 1990, the World Health Organisation (WHO) stated that “Because of considerable variation among individuals in sensitivity to TOCP, it is not possible to establish a safe level of exposure” and “TOCP are therefore considered major hazards to human health (9).
Although it is claimed that the para and meta isomers are not known to be toxic to humans (9), a recent article suggests that the widespread belief that only ortho isomers of TCP are dangerous is invalid (10).
A recent study suggests that the combined neurotoxicity measured on a cellular level is similar for the different TCPs. However, the clinical implications of the study are uncertain as the TCP concentrations used are well above current exposure levels in cabin air indicating limited neurotoxic health risk (11).
The reported concentration of TCP used in most aircraft engine oils is less than 3%, of which the ortho isomers constitute less than 0.2% of the total TCP. This results in an overall concentration of ortho isomers of less than 0.006% of the total engine oil (9).
There have been no publicly available sampling data collected during a bleed air contamination event on commercial aircraft. However, wipe sampling data has identified TCPs on aircraft cabin and flight deck walls (6). On the other hand, it has been pointed out that the presence of TCP is widespread and will even be found in wipe samples taken in buildings and other public places (9,12).
A study from 2013 investigated a total of 332 urine samples of pilots and cabin crew members in conventional passenger aircraft, who reported fume/ odor during their last flight. None of the samples contained the ortho isomers of TCP above the limit of detection (LOD). The authors concluded that health complaints reported by aircrews could hardly be addressed to exposure to the ortho isomers of TCP in cabin air (13).
The aviation industry claim that engine oil does not contain sufficient quantities of TCPs to cause long-term damage (14).
TurboNycoil 600 oil is developed by a French company named NYCO. It is now used by many military agencies worldwide and its use on commercial engines is growing. Unlike most other oils, it does not contain TCP at any measurable quantity (15).
The Role of Filtration
Bleed air is cooled but not cleaned (ie, filtered) before being mixed with recirculated cabin air (1).
However, recirculated air is cleaned using high-energy particulate air (HEPA) filtration. HEPA filters are designed to capture particles but not gases and vapors, which pass directly through the filter.
Aerosols collected via HEPA filtration include dust, fibers, bacterial cells, fungal spores, and pollen grains As viruses are among the smallest of microorganisms, ranging in size from 0 02 to 0 3 μm in diameter, they are too small to be captured by HEPA filters (1).
How Often Do Air Quality Events Occur?
When it comes to air quality events, there is no standardized incident reporting system in use for either passengers or crew. Hence, the frequency of fume events may be difficult to determine.
According to several data obtained from three US airlines, frequency estimates of bleed air contamination events range from 0.09 to 3.88 incidents per 1,000 flight cycles. Using the lowest estimate of 0.09 events per 1,000 flight cycles, there may be an average of two to three contaminated bleed-air events every day (6).
In 2007, the United Kingdom Committee on Toxicity (COT) undertook an independent scientific review of data submitted by the British Airline Pilots Association (BALPA) relating to concerns of its members about the possible health effects from oil fume contamination on commercial jet aircraft. The COT estimated that cabin air quality events occur on roughly 0.05% of flights (~1 in 2000)(8).
The Allied Pilots Association (APA), which represents American’s pilots, has cited as many as 20,000 fume incidents over the past decade, or about five per day (16).
A study published 2016 found that the contamination events were widely distributed across nearly all common models of aircraft (17).
The Allied Pilots Association (APA) has cited as many as 20,000 fume incidents over the past decade or about five per day.
Adverse Health Effects of Air Quality Events
The lack of a standardized protocol for the medical investigation of crew and passengers following air quality incidents means that consistent data is difficult to obtain.
The most common adverse effects reported following air quality events area acute respiratory symptoms and neurological symptoms. Psychiatric symptoms appear to be fairly common as well.
Among the symptoms reported are upper airway breathing problems (shortness of breath, wheezing, eyes, nose or throat irritation), performance decrement, tremor, memory impairment, headache, vision problems, nausea, fatigue, exhaustion, confusion, disorientation, anxiety, sleep disturbance, depression, chest pain, palpitations, and dizziness (6,10).
Individual susceptibility to damage by TCP exposure appears to be highly variable which may help explain why not all aircrew appear to be equally affected by fume events (10).
Short- and Long-Term Effects of Air Quality Events
There is abundant evidence of the continuous leakage of lubricating oil and hydraulic fluid into aircraft cabin air at all times (18). However, when analyzed in cabin air, the concentration of toxic substances has in most cases been too low to raise any health concerns.
Although the acute health effects of air quality events have been fairly well described, the impact of chronic, continual, low-dose exposure is still a matter of debate. Repeated exposure could explain the apparent differential vulnerability often described between aircrew and passengers.
In most cases of air quality events, symptoms improve and resolve within a few weeks. However, in some instances, such events appear to result in chronic adverse health effects.
Some airline workers may even have recurrent symptoms on return to work due to re-exposure to contaminants in the aircraft environment (6).
Respiratory symptoms appear to be the most common initial symptoms following air quality incidents. Although they often resolve quickly, irritant-Induced asthma may persist for more than 3 months following the exposure episode (6).
Neurological and psychiatric symptoms may in some cases be more persistent. These include headaches, confusion, loss of balance, lightheadedness, muscle weakness, movement disorders, numbness, paraesthesias, cognitive dysfunction, post-traumatic stress disorder (PTSD), emotional lability, depression, sleep and anxiety disorders (6).
Other long-term effects include persistent gastrointestinal problems, increased sensitivity to chemicals, myalgias, arthralgias, palpitations, and unusual fatigue (6).
Aerotoxic syndrome is a phrase coined by Chris Winder and Jean-Christophe Balouet in 2000, to describe their claims of short- and long-term ill-health effects caused by contaminated cabin air (19).
Although not well defined, the syndrome is supposed to cover most of the symptoms mentioned above associated with severe air quality events or repeated exposure to cabin air contaminants.
British ex-pilot John Hoyte founded the Aertotoxic Association in 2007. Hoyte is also an author of a book called “Aerotoxic Syndrome: Aviation’s Darkest Secret” published in 2014 (20).
The Aerotoxic Association’s primary role is to support aircrew and passengers whose short and long-term health have been affected by toxic oil fume exposure in the confined space of commercial jets and inform the public of the harm associated with poor aircraft cabin air quality and the causative link to aerotoxic syndrome (21).
Bearnairdine Beaumont is an author of a book called “The Air I Breathe – It’s Classified: A True Story and Top Guide to the Aerotoxic Syndrome Phenomena Experienced by Aircrew and Passengers“. In the book, Beaumont highlights the dangers, toxicity and neurotoxic properties of compounds contained in jet engine oils.
The Aerospace Medical Association has reviewed the available scientific evidence and concluded that there was insufficient consistency and objectivity to support the establishment of a clearly defined syndrome. The US National Academy of Sciences performed a similar review and reached the same conclusion, as did the Australian Government CASA Expert Panel on Aircraft Air Quality in 2012 (9).
Thus, the concept of the “Aerotoxic Syndrome” as a well defined entity is not recognized by the aviation medicine community.
In a review published 2014 (9), Professor Michael Bagshaw writes that the “reported symptoms are wide-ranging with insufficient consistency to justify the establishment of a medical syndrome. It has been noted that many of the acute symptoms are normal symptoms experienced by most people frequently; some 70% of the population experience one or more of them on any given day.”
In his report, Dr. Bagshaw also claims that “so far as scientific evidence has been able to establish to date, the amounts of organophosphates to which aircraft crew members could be exposed, even over multiple, long-term exposures, are insufficient to produce neurotoxicity.”
Other Factors to Consider During Suspected Air Quality Events
In some cases, symptoms attributed to air quality incidents may be caused by hyperventilation.
Hyperventilation, sometimes called over breathing, is breathing in excess of what the body needs.
Hyperventilation may be a normal response to emotional stress. The triggers for hyperventilation may be of physical, mental, emotional or environmental nature.
In the aviation environment, it is recognized that hyperventilation is a common condition.
For pilots and cabin crew, the following in-flight triggers may cause hyperventilation (22):
The symptoms associated with hyperventilation include (22):
Paresthesia (“pins and needles” – tickling, tingling, burning, pricking, or numbness) especially in the extremities.
Increased heart rate
Muscle spasms and tics
There is an overlap between the wide range of symptoms attributed to contamination of cabin air and those caused by hyperventilation. Hyperventilation may also be triggered by an air quality incident.
However, it would be nonsensical to suggest that hyperventilation may explain all cases of suspected air quality events.
The Nocebo Effect
The nocebo effect describes an illness, often with physical symptoms and signs, which is triggered through psychological processes in response to a perceived harmful exposure. The phenomenon is analogous to a placebo effect in which symptoms improve in response to a perceived beneficial exposure (22).
Hence, awareness of irritation or an odor on board may trigger a psychologically mediated nocebo effect. Such a response may also be triggered by observing other flight personnel or passengers feeling unwell or experiencing symptoms possibly attributed to air quality issues.
The Bottom Line
Reports of possible cabin air contamination onboard aircraft on commercial flights have become increasingly common in recent years. Such incidents are often described as fume events or air quality incidents.
It is estimated that upto five such events occur every day in the United States.
Contamination of bleed air used to pressurize and ventilate..
High blood pressure (BP), also called hypertension, increases the risk of heart disease, stroke, and kidney disease. It is one of the most important causes of premature death worldwide.
In 2025, an estimated 1.56 billion adults will be living with hypertension (1). According to the World Health Organization (WHO), hypertension kills nearly 8 million people every year.
Overall, approximately 20% of the world’s adults are estimated to have hypertension. In 1991, the National High Blood Pressure Education Program (NHBPEP) estimated that 43.3 million adults had hypertension in the United States (2). The prevalence dramatically increases in patients older than 60 years.
It is crucial for health professionals and patients to understand how BP is measured, how hypertension is diagnosed and what are the most common pitfalls to avoid when estimating if hypertension is present or not.
1. The Definition of Blood Pressure
Each time the heart muscle contracts it pumps blood into the arteries to supply the tissues and organs of the body with oxygen-rich blood. BP is the measure of pressure in the arteries. This may be compared to the pressure of water in a garden hose, except that the arterial wall is a living tissue.
BP is recorded as two numbers, e.g., 125/80 millimeters of mercury (mm Hg). The first number is the systolic pressure, that is when the heart muscle contracts and blood is pumped into the arteries. The lower figure, the diastolic pressure, is the pressure when the heart is relaxing and filling up with blood, between strokes.
2. The Definition of Normal Blood Pressure and Hypertension
The following is the most widely used classification of BP and hypertension (3):
Normal: Systolic BP lower than 120 mm Hg, diastolic BP lower than 80 mm Hg
Prehypertension: Systolic BP 120-139 mm Hg, diastolic BP 80-89 mm Hg
Stage 1 hypertension: Systolic BP 140-159 mm Hg, diastolic BP 90-99 mm Hg
Stage 2: Systolic BP 160 mm Hg or greater, diastolic BP 100 mm Hg or greater
In 2017, the American College of Cardiology/American Heart Association (ACC/AHA) updated their guidelines for the prevention, detection, evaluation, and management of high blood pressure in adults by eliminating the classification of prehypertension and dividing it into two levels (4).
Normal: Less than 120/80 mm Hg;
Elevated: Systolic between 120-129 and diastolic less than 80;
Stage 1: Systolic between 130-139 or diastolic between 80-89;
Stage 2: Systolic at least 140 or diastolic at least 90 mm Hg;
Hypertensive crisis: Systolic over 180 and/or diastolic over 120, with patients needing prompt changes in medication if there are no other indications of problems, or immediate hospitalization if there are signs of organ damage.
3. Understanding How Blood Pressure Changes With Age
A progressive rise in BP is seen with increasing age.
However, age-related hypertension appears to be predominantly systolic rather than diastolic. The systolic BP rises into the eighth or ninth decade, whereas the diastolic BP remains constant or declines after age 40 years. Hence, pulse pressure, the difference between the systolic and diastolic blood pressure, increases with age
The prevalence of hypertension grows significantly with increasing age in all sex and race groups (5). It has been estimated that the incidence of hypertension increases by approximately 5% for each 10-year interval of age.
4. The Circadian Pattern of Blood Pressure
Blood pressure is typically lower at night, during sleep and then starts to rise a few hours before we wake up. It reaches a peak in the morning shortly after awakening. Then in the late afternoon and evening, BP starts dropping again.
Blood pressure is typically lower at night, during sleep and then starts to rise a few hours before we wake up. It reaches a peak in the morning shortly after awakening.
The onset of many acute cardiovascular and cerebrovascular events shows a daily pattern, with the highest incidence of morbidity and mortality in the early morning hours. Strong, although circumstantial, evidence suggests that the early morning surge in blood pressure may contribute to the onset of acute cardiovascular episodes (6).
5. Understanding How Blood Pressure Is Measured
Correct measurement of BP is essential in the diagnosis of hypertension. BP machines have to be properly calibrated, and appropriate cuff sizes have to be selected.
The patient should be in a seated position with the back supported and legs uncrossed. The diastolic pressure may be higher by 6 mm Hg if the back is unsupported and the systolic pressure may be raised by 2-8 mm Hg if the legs are crossed (7).
The patient should not talk during the procedure as it can raise the measured value by as much as 8-15 mm Hg (8)
Here is what you can do to ensure a correct reading (9):
Don’t drink a caffeinated beverage or smoke during the 30 minutes before the test.
Sit quietly for five minutes before the test begins.
During the measurement, sit in a chair with your feet on the floor and your arm supported so your elbow is at about heart level.
The inflatable part of the cuff should completely cover at least 80% of your upper arm, and the cuff should be placed on the bare skin, not over a shirt.
Don’t talk during the measurement.
Have your blood pressure measured twice, with a brief break in between. If the readings are different by 5 points or more, have it done a third time.
Checking blood pressure at home (JAMA. 2017;318(3):310. doi:10.1001/jama.2017.6670)
6. Different Measurement Strategies For Detecting Hypertension
There are three different measurement strategies to detect hypertension:
Ambulatory BP-monitoring (ABPM)
Home BP monitoring
Although screening for hypertension is often performed at the doctor’s office, many individuals with high BP measurements at the office will not have hypertension upon further testing (10). This is commonly due to white coat hypertension.
ABPM monitoring is the preferred method for detecting hypertension. If ABPM is not feasible, home BP monitoring may be used.
7. White Coat Hypertension
It is essential to understand that BP is not a fixed number. BP varies throughout the day in response to what we are doing and what is happening around us.
Some people with normal BP find that it spikes when they visit the doctor. This condition is called white coat hypertension or the white coat effect (also called isolated clinic or office hypertension).
The white coat effects will often happen because we are nervous about having our BP tested by a doctor or nurse. Most of us tend to feel tenser in medical settings than we do in surroundings that are familiar to us, although we do not always notice it.
Sometimes the white coat effect may be powerful, making it impossible to establish a correct resting blood pressure in the doctor’s office. Hence, it is imperative not to rely on office-based BP measurements when diagnosing hypertension.
People with white coat hypertension may sometimes be at increased risk for cardiovascular events and can go on to develop hypertension. Hence, close follow-up is recommended (11).
The white coat effect may persist for years. It may be avoided by using ABPM or home-based BP-monitoring.
8. Ambulatory Blood Pressure Monitoring (ABPM)
Ambulatory blood pressure monitoring (ABPM) is performed by using a small digital BP machine, usually attached to a belt around the body and connected to a cuff around the upper arm.
ABPM is performed by using a small digital BP machine, usually attached to a belt around the body and connected to a cuff around the upper arm. The device takes BP measurements regularly over a 24-48 hour period, usually every 15-20 minutes during daytime and every 30 to 6 minutes during nighttime.
The BP measurements are recorded on the device, and the average day (diurnal) and night (nocturnal) BPs are determined from the data by a computer.
ABPM has been considered to be the reference standard for the diagnosis of hypertension and is a better predictor of cardiovascular disease risk as compared with conventional office-based measurements (9).
9. Reference Values for Ambulatory Blood Pressure Monitoring (ABPM)
When ABPM is used, hypertension is defined as a 24-hour average BP greater to er equal to 125/75 mm Hg (10).
A 24 hour mean BP during ABPM of 115/75 is considered normal and mean BP higher than 125/75 is considered too high.
When looking at individual measurements, normal ambulatory blood pressure should not be above 135/85 mm Hg during the day and not above 120/70 mm Hg at night. Levels above 140/90 mm Hg during the day and 125/75mm Hg at night should be considered as abnormal (9).
10. Dipping and Non-Dipping
The average nighttime BP is approximately 15 percent lower than daytime values. People who undergo this normal physiological change are described as dippers.
Failure of the blood pressure to fall by at least 10 percent during sleep is called non-dipping.
The underlying mechanisms of non-dipping are unknown, but melatonin may play a role (11).
Non-dipping may be associated with increased cardiovascular risk (12).
11. Home Blood Pressure Measurements
Relatively inexpensive semiautomatic devices may be used for home BP measurements. These measurements correlate more closely with the results of 24-hour ABPM than with BP taken in the clinician’s office (13).
The optimal schedule for home blood pressure measurements is unclear. Evidence suggests that 12-14 measurements should be obtained to assess blood pressure correctly. These should include both morning and evening measurements during one week (14).
While seated, the patient should take two measurements (separated by one to two minutes) in the morning and the evening for at least three, and preferably seven consecutive days. Measurements from the first day should be discarded; the home blood pressure is defined as the average of all remaining measures.
It is important to acknowledge that home BP measurements may vary widely depending on factors such as stress caffeine intake, smoking, exercise and natural circadian variation.
12. Office-Based Blood Pressure Measurements
Despite their limitations, office-based BP measurements continue to be the primary technique used worldwide for the detection and management of hypertension.
Clinicians and patients should be aware of the possibility of white coat hypertension.
Multiple measurements on different days may be necessary. The patient should sit quietly for five minutes before the BP is measured. Patient position, cuff size, and cuff placement are all important.
It is crucial for health professionals and patients to understand how BP is measured, how hypertension is diagnosed and what are the most common pitfalls to avoid when estimating if hypertension is present or not.
Office-based BP measurements are of limited value because of the frequency of white coat hypertension.
Ambulatory blood pressure measurements (ABPM) are considered to be the reference standard for the diagnosis of hypertension and provide a better predictor of cardiovascular disease risk as compared with conventional office-based measurements.
It is important to acknowledge that reference values for ABPM measurements are different from those used for office-based measurements.
If not ABPM is feasible, home BP monitoring may be used. Educating patients about when and how to perform such measurements is of crucial importance.
Melatonin is a hormone that regulates sleep, wakefulness, and circadian rhythms in humans.
Circadian rhythm describes the sleep/wake cycle, a biological clock that runs in our brain and cycles between sleepiness and alertness. It explains why we may feel energized or sleepy at around the same time each day.
We all know that sleep is crucial for our health and wellbeing. But, sadly, millions of people suffer from sleep disorders. It is believed that about one-third of Americans suffer from some sleep problems.
The most common issues are waking up in the morning feeling drowsy or tired, followed by waking up in the middle of the night, difficulty going back to sleep after waking up and difficulty falling asleep initially (1).
Insomnia is defined as difficulty falling asleep or staying asleep, even when we have the chance to do so. People with insomnia are usually unhappy with their sleep and often experience fatigue, low energy, difficulty concentrating, mood disturbances, and decreased performance in work or at school (2).
Insomnia can be acute (short-term) or chronic (ongoing)(3). Acute insomnia is often caused by situations such as stress at work, family issues or a traumatic event. This type of insomnia may last for days or weeks. Chronic insomnia lasts for a month or longer.
There are several ways to deal with insomnia. Treating a possible underlying cause is usually the first step. This may include avoiding caffeine, tobacco and other stimulants. Alcohol and certain medicines may also disrupt sleep.
Cognitive behavioral therapy may be helpful (4). Such treatment targets thoughts and actions that may disrupt sleep and encourages good sleep habits.
Several medicines are available to treat insomnia, including over-the-counter (non-prescription) and prescription medications. Such sleep aids may cause side effects such as daytime sedation and dizziness, and some are associated with risk of tolerance, dependence, and addiction.
Melatonin is often recommended to treat insomnia. It is available as a food supplement in health food stores. No substantive risks from melatonin use have been reported. However, several questions remain about its efficacy which may depend on drug dose and formulation, as well as the timing, frequency, and duration of administration (5).
1. What Is Melatonin?
Melatonin (N-acetyl-5-methoxy tryptamine) is a hormone produced by the pineal gland in animals and humans.
The pineal gland is a small gland located deep in the center of the brain
Three centuries ago, the French philosopher René Descartes described the pineal gland as “the seat of the soul.” However, it was not until the late 1950s that melatonin was identified (6)
Melatonin is synthesized from the essential amino acid tryptophan.
2. What Foods Contain Tryptophan?
Essential amino acids cannot be made by the body. As a result, they must come from food.
The highest levels of tryptophan are often found in complete proteins like red meat, fish, poultry, milk, and eggs. While most plant sources do not contain as much tryptophan as meat or dairy products, there are many plant-based options available including chickpeas, cashews, cauliflower, kidney beans, and quinoa (7).
Serotonin is a brain neurotransmitter, and an essential biochemical messenger and regulator. The metabolism of tryptophan into serotonin requires nutrients such as vitamin B6, niacin, and glutathione.
3. What Is the Relationship Between Tryptophan, Serotonin, and Melatonin?
The biosynthesis of melatonin is initiated by the uptake of the uptake of tryptophan into the pineal gland.
The cells of the pineal gland convert tryptophan to another amino acid, 5-hydroxytryptophan, through the action of the enzyme tryptophan hydroxylase and then to 5-hydroxytryptamine (serotonin) by the enzyme aromatic amino acid decarboxylase (8).
Serotonin concentrations are higher in the pineal than in any other organ or in any brain region. There is a striking diurnal rhythm with serotonin remaining at a maximum level during the daylight hours and falling by more than 80% soon after the onset of darkness as the serotonin is converted to melatonin, 5-hydroxytryptophol and other methoxyindoles (8).
Tryptophan is an essential amino acid
Tryptophan is a precursor for the formation of serotonin and melatonin
The pineal gland converts tryptophan to serotonin which is then converted to melatonin
Serotonin levels are maximal during daylight hours
Serotonin levels drop after the onset of darkness as the pineal gland converts most of the serotonin to melatonin
Serotonin levels are maximal during daylight hours Serotonin levels drop after the onset of darkness as the pineal gland converts most of the serotonin to melatonin
4. When Does the Pineal Gland Secrete Melatonin?
Melatonin secretion manifests a circadian rhythm. Secretion is low during daylight, ascending after the onset of darkness, peaking in the middle of the night between 11 PM and 3 AM, and then falling sharply before the time of light onset (9).
Interestingly, high nocturnal concentrations of melatonin are characteristic of both diurnally active species (like humans), in which high levels promote sleep, and nocturnally active ones (like rats), in which melatonin has no apparent relationship to sleep (10).
The melatonin produced by the pineal gland diffuses into the cerebrospinal fluid and the bloodstream. Melatonin is highly lipid soluble and diffuses freely across cell membranes. It travels in blood primarily bound to the protein albumin.
5. Is There a Seasonal Variation in Melatonin Concentration?
Melatonin secretion by the pineal gland appears to have a seasonal rhythm. Hence, melatonin levels are higher in the fall and winter and lower in the spring and summer (6).
People with seasonal affective disorder (SAD) typically feel sad or down during the winter months. In some cases, this may develop into a subtype of clinical depression that lasts throughout the late fall and winter months.
Excessive duration of melatonin secretion has been implicated in SAD, but researchers are far from settled on this theory.
Some studies have shown that people with SAD may have increased duration of melatonin secretion in the early morning hours. This would explain why people with SAD have difficulty waking up and don’t feel alert in the morning. Nevertheless, low-dose melatonin taken at night may sometimes be useful in improving mood in patients with SAD (11).
6. Does Age Affect Melatonin Levels?
There is a marked age variation in melatonin secretion by the pineal gland.
Melatonin Secretion starts during the third or four months of life, coincident with sleeping at nighttime becoming more common. It then increases rapidly to peak at ages two and three years, then declines slightly to a plateau that lasts throughout early adulthood (10).
Melatonin secretion declines with advancing age. At the age of 70, nocturnal concentrations are only a quarter or less of what they are in young adults (12).
One rationale for administering supplemental melatonin to older adults with sleep disorders is to compensate for the age-related decline in melatonin secretion.
7. What Are Melatonin Sleep Aid Supplements?
In the United States, melatonin is defined by the US Food and Drug Administration as a dietary supplement. Hence it can be purchased at any dose without a prescription.
In the European Union, melatonin is defined as a prescription drug and is not available over-the-counter. Based on the currently available evidence, 1 mg of melatonin is recommended close to bedtime to reduce sleep onset latency.
Melatonin supplements are available as pills, liquids, and chewable. You may find them in natural or synthetic forms.
Despite claims to the contrary, all of the melatonin sold in the United States is of synthetic origin (10).
As the sale of melatonin is not regulated in the US, very high doses can be sold and may contain additives with potential side effects.
Unlike with many other sleep medications, you are unlikely to become dependent on melatonin, have a diminished response after repeated use (habituation) or experience a hangover effect (13).
8. Is it Scientifically Proven that Melatonin Can Help You Sleep?
Yes, indeed it is. Several studies have shown that melatonin may positively affect several measures of sleep.
A systematic analysis of several placebo-controlled studies showed that melatonin treatment significantly reduced sleep onset latency, increased sleep efficiency, and increased total sleep duration (14).
9. What Doses of Melatonin Should be Used to Promote Sleep?
A dose of 0.1 – 0.3 mg of melatonin before sleep is adequate. This dose will raise the nocturnal plasma concentration of melatonin into the normal range observed in young adults (15).
Although melatonin is generally considered relatively nontoxic, it is worth keeping in mind that some marketed doses, such as 10 mg, can raise plasma concentrations 60 times their normal values (16).
Very high levels of melatonin may be associated with side effects such as daytime sleepiness, tiredness, and hypothermia.
10. When Is the Best Time to Take Melatonin?
If you have trouble falling asleep you should take melatonin at night. Taking melatonin 30-60 minutes before you go to sleep is a good option.
People who are night owls and usually go to bed late may want to take melatonin 2-3 hours before the desired bedtime, at least if they want to go to sleep earlier than usual.
11. How Can the Function of the Biological Clock (Circadian Pacemaker) Be Measured?
The circadian rhythm of melatonin production typically reflects our biological clock, sometimes called the circadian pacemaker.
A substantial number of studies have shown that, within this rhythmic profile, the onset of melatonin secretion under dim light conditions (the dim light melatonin onset or DLMO) is the single most accurate marker for assessing the circadian pacemaker (17).
The DLMO has been used to assess whether an individual is entrained (synchronized) to the 24-h light-dark cycle or is free-running, or whether an entrained individual is abnormally phase-advanced or phase-delayed (18).
Phase-advanced individuals have DLMOs that occur abnormally early in the evening, usually between 6 and 8 p.m. Phase-delayed individuals have DLMOs that occur after 10 p.m.
Winter depressives tend to have slightly delayed DLMOs. These patients also have difficulty waking up in the morning, a clinical finding that is associated with phase-delayed circadian rhythms (19). These patients are similar to individuals who have delayed sleep phase syndrome (DSPS). Characteristic of DSPS is difficulty falling asleep before 1 a.m.
Patients who tire easily in the evening and cannot extend their sleep past 3-5 a.m. often have advanced sleep phase syndrome (ASPS).
12. Can Melatonin Be Used to Phase Shift the Human Circadian Clock?
Air travelers have transient DSPS after flying eastward and transient ASPS after flying westward.
Hence, when traveling eastward, it will be more difficult to fall asleep in the evening and harder to get up in the morning. When going westward, staying awake in the evening will be more difficult, and we’ll be likely to wake up early in the morning.
Night workers have ASPS during their work weeks and DSPS on their off-work days.
Melatonin, even when administered at a physiological dose (0-3- 0.5 mg) can shift our circadian phase (20). This could promote the adaptation to air travel and night work.
13. Can Melatonin Be Used to Phase To Prevent and Treat Jet Lag?
Melatonin has been widely studied as a jet lag remedy. Melatonin may aid sleep during times when you wouldn’t normally be resting which may be helpful against jet lag.
According to an analysis of Cochrane data, melatonin is remarkably effective in preventing or reducing jet lag, and occasional short-term use appears to be safe (22). It should be recommended to adult travelers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet lag on previous journeys. Travelers crossing 2-4 time zones can also use it if need be.
According to this data, daily doses of melatonin between 0.5 and 5 mg are similarly effective, except that people fall asleep faster and sleep better after 5 mg than 0.5 mg. Doses above 5 mg appear to be no more effective.
The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low.
14. Can Melatonin Improve Daytime Sleep In Night-Shift Workers?
There is substantial evidence that the prevalence of sleep disorders is a significant occupational health problem among night shift workers.
Melatonin may be an effective treatment for shift workers with difficulty falling asleep.
One study found that melatonin may improve daytime sleep in night-shift workers (23).
Another study found that 5 mg of melatonin taken 30 minutes before nighttime sleep reduced sleep onset latency among nurses following recovery from night work (24).
15. What Are the Side Effects of Melatonin?
Even though melatonin is an unregulated drug in many countries and is commonly used in excessive doses, adverse effects seem to be relatively uncommon.
Drowsiness, headache, fragmented sleep, dizziness, and nausea are among the side effects that have been described.
It is not known whether melatonin will harm an unborn baby or a nursing infant. Hence, it should be avoided during pregnancy and breastfeeding.
Furthermore, there have been no long-term safety studies of the use of melatonin in children and adolescents.
Also, melatonin supplements can interact with various medications, including anticoagulants and antiplatelet drugs, anticonvulsants, contraceptive drugs, diabetes medications and drugs that suppress the immune system.
Major depression affects more than 16 million American adults each year (1). It can occur to anyone, at any age. And, importantly, depression is not a personal weakness but a severe medical illness.
Of course, we all have times when our mood is low. Gloom, heartache, melancholy, woe, desolation. These are all parts of life’s journey and fortunately most often normal temporary reactions to daily events. But, at what stage should such feelings be defined as clinical depression?
The British author and poet, Giles Andreae who himself has battled depression once said: “Thinking you’ve had depression makes about as much sense as thinking you’ve been run over by a bus. Trust me – you know when you’ve got depression (2)”
Although this is not entirely true, it emphasizes the difference between clinical depression and occasional episodes of low mood. However, unfortunately, too many people don’t acknowledge their depression or think it isn’t serious or even believe that it is some personal weakness.
Only about a third (35.3%) of those suffering from severe depression seek treatment from a mental health professional (3). Hence, it is estimated that as many as two-thirds of people with depression do not realize that they have a treatable illness and do not seek treatment.
According to The American Psychiatric Association, “depression (major depressive disorder) is a common and serious medical illness that negatively affects how you feel, the way you think and how you act. Fortunately, it is also treatable. Depression causes feelings of sadness and/or a loss of interest in activities once enjoyed. It can lead to a variety of emotional and physical problems and can decrease a person’s ability to function at work and home” (4).
Hence, we might conclude that depression reflects long and persistent periods of low mood without reason? But, that’s a misinterpretation. The truth is that there is a reason. That reason is the disease we call depression.
The British actor and writer Stephen Fry has talked openly about his depression. He says: “Why should I be depressed? I’ve got enough money. I’ve got a job. People like me. There is no reason to be depressed. That’s as stupid as saying there is no reason to have asthma or there is no reason to have the measles. You know you’ve got it. It’s there. It’s not about reason.
Depression is often considered to be a mood disorder. Fry says: “To me, mood is like the weather. Weather is real. It is absolutely real: when it rains, it rains – you get wet, there is no question about it. It is also true about weather that you can’t control it; you can’t say if I wish hard enough it won’t rain. It is equally true that if the weather is bad one day, it will get better and what I had to learn was to treat my moods like the weather.”
1. Depressive Mood
Persistent sad, anxious or “empty” mood is an essential feature of major depression.
However, frequently those who have suffered from depression describe their depressive mood in a more specific manner. It is not just about feeling sad all the time. It is somewhat different and usually much worse.
In fact, people with depression not always feel sad. They may be able to speak with their friends and have a laugh. On the outside, it may look like there’s nothing wrong. But inside, there is something missing. There is an emptiness, so hard to describe and so hard to understand unless you have experienced it yourself.
Let me quote Stephen Fry again: “There comes a time when the blankness of the future is just so extreme, it’s like such a black wall of nothingness. Not of bad things like a cave full of monsters and so, you’re afraid of entering it. It’s just nothingness, the void, emptiness and it is just horrible.”
Fry even goes further and says: “It’s like contemplating a future-less future and so you just want to step out of it. The monstrosity of being alive overwhelms you.”
Depression is often associated with anxiety. Both are facilitated by stress, either recent or dating back to childhood (5). Up to 70 percent of patients with depression experience anxiety (6).
Anxiety may be described as a feeling of worry, nervousness, or unease about something with an uncertain outcome.
Today, many experts believe that depression and anxiety are not two disorders that coexist but two faces of one disorder (7).
Often, anxiety precedes depression, sometimes by several years. Typically the onset of anxiety is in late childhood or early adolescence. Depression usually begins a few years later with typical onset in the mid-20s (8). But, of course, depression may occur at any age.
One person suffering from depression and anxiety wrote (9): I’ve always lacked self-confidence, even before my anxiety disorder was identified. I try to mingle with the best of them, but at the same time on the inside, I’m an intolerable nervous wreck and always wish I was at home watching repeats of “Friends” with a slab of fudge cake, even when I’m socializing with my nearest and dearest. Sadly, I don’t think this will ever change. So when I’m at that point where I’m trying just to leave the house, let alone do anything adventurous, my fragile mind always says “But, why? Why bother? You’re going to fail at this anyway?”
In fact, isolation may become quite severe. Simple tasks such as going to the supermarket may become a major hurdle.
3. Loss of Interest or Pleasure in Activities Once Enjoyed (Anhedonia)
The word Anhedonia describes the inability to experience pleasure from activities usually found enjoyable, e.g., exercise, hobbies, and social interactions. In Greek, anhedonia directly translates to “without pleasure.”
Most patients with depression have anhedonia. It is a crucial feature of major depression. Events and activities we used to enjoy become less interesting or fun. We may even lose interest in our friends. Libido and interest in sex often decrease as well.
Some experts suggest that anhedonia comes not from a reduced capacity to experience pleasure, but instead from an inability to sustain good feelings over time. In other words, maybe pleasure is experienced fully, but only briefly, not long enough to sustain interest or involvement in life’s good things (10).
In anhedonia, the simple and satisfying sensation of joy seems to be lacking.
Following his experience with depression, Giles Andrea wrote: “And if depression has taught me one thing, it is this: what a rare and beautiful treasure is the simple human gift of joy. For me now, joy – our capacity to delight in one another and the world – is the reason why we are here. It is as simple as that. And I feel compelled to spread the word (2).”
Anhedonia may promote social withdrawal and negative feeling towards yourself and others. Emotional abilities may be reduced, and there may be a tendency to show fake emotions. We may struggle to adjust to social situations and our interest in intimacy may diminish.
Sometimes, anhedonia is divided into social anhedonia (a general disinterest in social contact), and physical anhedonia (an inability to feel pleasure from things likes eating, touching or sex)(11).
4. Fatigue or Loss of Energy
Contrary to many other medical symptoms, fatigue is an entirely normal phenomenon in particular situations. We all become tired, but it usually gets better by rest or sleep. However, chronic fatigue as a medical symptom is typically persistent and not relieved by rest (12).
Chronic fatigue is prevalent among patients with depression. It is often described as feeling tired all the time, exhausted or listless. Some people with depression experience total lack of energy sometimes called ‘anergia’.
Fatigue and depression seem to have a circular relationship. For some, fatigue will come first; for others, depression will come first, but for most, it will probably be unclear (13). The fatigue may lower self-esteem and make the depression worse, leading to more fatigue.
If the fatigue that comes with depression becomes overpowering, basic tasks such as getting out of bed and walking may be exhausting.
The symptoms of fatigue can affect physical, cognitive, and emotional function, impair school and work performance, disturb social and family relationships, and increase healthcare utilization (14).
5. Feelings of Worthlessness or Excessive Guilt
A study of patients with major depression published 2015 showed that self-blaming emotions occurred in more than 80% of patients with self-disgust/contempt being more frequent than guilt, followed by shame (15).
The majority (85% of patients) reported feelings of inadequacy and self-blaming emotions as the most bothering symptoms compared with 10% being more distressed by negative emotions towards others.
Patients with depression often tend to misinterpret events or minor setbacks as evidence of personal failings (16).
A patient with depression has described her feelings in the following manner (17):
“I should be a spy; I am so good at leading a double life. I can put on a smile, muster up a good conversation (after ignoring a few calls and messages), but the reality is, all those “normal,” happy interactions exhaust me, and for that, I feel guilty.
I feel guilty that I want to scream at my boyfriend who is just trying to be understanding. I feel guilty that I cause those closest to me to worry. My parents, my partner, my family, and friends, all of them try to support me, to ensure I don’t get too low. How do I tell them it isn’t them and no matter what they do often I just feel low? I feel guilty that their efforts to help sometimes just make it worse.
I feel guilty for canceling plans last-minute. I mean to go, I want to go, but often I just don’t have the strength. I am brilliant at making excuses, but the shame I feel for letting people down is ever-present.
I even feel guilty for feeling guilty. Maybe some other people understand this warped way of thinking. I would tell anyone else with depression to not be so hard on themselves, to acknowledge their efforts. But to me, I just feel guilty.”
6. Sleep Disturbance (Insomnia and Hypersomnia)
Several types of sleep disorders may occur in patients with depression. The term insomnia is used often used to describe the symptoms associated with these sleep disorders.
Insomnia may be a difficulty falling asleep, waking up frequently during the night with difficulty returning to sleep, waking up too early in the morning, or merely an unrefreshing sleep. It is not defined by the number of hours slept but reflects the satisfaction with sleep. Insomnia is often associated with tiredness, lack of energy, difficulty concentrating, and irritability.
Depression may be associated with difficulty getting to sleep (initial insomnia). Waking in the middle of the night (middle insomnia) or earlier than usual (terminal insomnia) with difficulty turning to sleep is common. Prolonged nighttime sleep or daytime sleeping (hypersomnia) may occur as well.
About three-quarters of depressed patients have insomnia symptoms, and hypersomnia is present in about 40% of depressed young adults and 10% of older patients, with a preponderance of females (18).
Disturbed sleep is a very distressing symptom which has a significant impact on quality of life in depressed patients (19).
Many patients with depression wake up prematurely in the early morning hours, unable to get back to sleep. This early-morning awakening is often associated with dysphoria and depressive thoughts, and sometimes there is an agitated, even a panicky feeling. This may often get better during the day and the evenings are often more comfortable.
7. Neurocognitive Dysfunction (Difficulty Concentrating, Remembering or Making Decisions)
Neurocognitive dysfunction is common in patients with depression (20).
Memory loss and an inability to focus or concentrate may be pronounced. Working memory, fluency, and planning and problem-solving abilities may be impaired.
People with depression often feel like they can’t focus. Comprehending what you are reading may become difficult and affect the ability to store information. This may negatively impact enjoyment when reading for pleasure.
The ability to receive information or directions may be impaired. We may appear easily distracted. This may affect performance at school and work. Sometimes these symptoms may be misinterpreted as lack of interest or consideration.
In most cases, neurocognitive dysfunction in depression is readily distinguished from that caused by dementia.
8. Change in Appetite and Body Weight
Reduced appetite and weight loss are common in patients with depression. However, increased appetite and weight gain may also occur.
Changes in eating habits are often related to other symptoms of depression, such as lack of energy and interest or pleasure from activities.
While a loss of appetite is common in depression, the sadness or worthlessness experienced by many patients may be associated with overeating (emotional eating). Emotional eating is eating in response to emotional rather than physical hunger.
Psychomotor disturbances that are common in depression include both agitation and retardation (16).
Psychomotor agitation is a series of unintentional, nonproductive or purposeless motions. In patients with depression, this may present as hand-wringing, pacing, and fidgeting.
Psychomotor retardation is a slowing down of thought and physical movements and may include slowing of body movements, thinking, and speech.
10. Thoughts of Suicide or Death
Depressed patients often experience recurrent thoughts of death. Suicidal ideation often occurs and there is a risk of suicidal attempt in some patients with depression (21).
Sometimes, suicidal ideation is passive. Patients often consider life not worth living and that their closest family and friends would be better off if the patient were dead.
In contrast, active suicidal ideation is marked by thoughts of wanting to die or commit suicide (16). There may be suicide plans and preparatory acts (e.g., selecting time and location, choice of method, or writing a suicide note). Such behavior indicates the patient is severely ill.
Suicidal ideation is usually preceded by hopelessness and negative expectations for the future. The patient may regard suicide as the only option to escape a never-ending and intense emotional and often physical pain
Alarmingly, many patients with suicidal ideation have not been recognized as having depression. In a large Canadian study, 48% of patients who had suicidal ideation and 24% of those who had made a suicide attempt reported not receiving care or even perceiving the need for care (22). The investigators concluded that future research should be directed toward finding better ways to identify these individuals and address barriers to their care and other factors that may interfere with their receiving help.
The annual suicide rate in the United States is approximately 13 per 100,000 individuals. Suicide is the tenth leading of cause of death. In 2014, the total number of suicide deaths in the United States was 42,773 (23). This equals 117 suicide deaths every day.
It is recognized that certain occupations and professions may be more susceptible to depression and suicide. Occupations that require frequent or difficult interactions with the public or clients, and have high levels of stress and low levels of physical activity seem to be at highest risk (24).
The medical profession has the highest risk of death by suicide of any profession or occupation. Other high control and highly regulated professions such as law enforcement, military, and the legal profession may be more likely to experience depression and suicidal behavior, and less likely to seek intervention because of the associated stigma and possible licensure implications (25).
Recent research suggests that suicide is three times more likely in individuals who have experienced a concussion, so occupations that might result in head injuries may be predisposed to suicide, with or without concomitant depression (26, 27).
Many individuals with depression have described their suicidal thoughts(27). Here are a few examples:
“It feels like you’re all alone and no matter what’s said to you, you feel like it’s not true or doesn’t matter. It feels like you just need to end it all because you’re so tired of fighting every single day.”
“I didn’t realize what I was feeling until I came out of it. It felt like I wasn’t breathing, I was drowning, and someone was holding my head under water. I was lost, alone and there was no other way out. No one understood me and no one ever would. When I finally broke free of the deep suicidal thoughts, I was able to see them for what they were, not before or during. I felt choked by the emotions and blinded by them.”
“A constant ache in my heart, my lungs, my wrists, my legs, my mind and the pit of my stomach. The ache that tells me nothing is sacred; everything is pointless. That nothing ever has or ever will matter. Why must I continue breathing? Why must I keep getting out of bed every day when I am so incredibly tired? Feeling utterly worthless, to the point that you wonder if your own children would be better off without you around.”
“The thought of death formed as a monster in my head. It is after me; I cannot run away from it. I don’t want to die, but I don’t want to live, either. The pain is too much strong, so I desperately think I cannot take another day. But deep down inside of me, I always have a tough wish to see another day — as a human instinct, I guess. I grabbed this very little feeling to go on. I hope everyone else will [too].”
“And if depression has taught me one thing, it is this: what a rare and beautiful treasure is the simple human gift of joy. For me now, joy – our capacity to delight in one another and the world – is the reason why we are here. It is as simple as that. And I feel compelled to spread the word.” Giles Andrea
Symptoms of depression may include the following:
Persistently sad, anxious, or empty moods
Loss of pleasure in usual activities (anhedonia)
Feelings of helplessness, guilt, or worthlessness
Crying, hopelessness, or persistent pessimism
Fatigue or decreased energy
Loss of memory, concentration, or decision-making capability
Poor abstract reasoning
Change in appetite or weight
Physical symptoms that defy diagnosis and do not respond to treatment – (very commonly pain and gastrointestinal complaints)
Thoughts of suicide, death, or suicide attempts
Poor self-image or self-esteem
To establish a diagnosis of major depression, a patient must express two of the first two itemsabove and at least five of the other symptoms listed. Such disturbances must be present nearly daily for at least two weeks (25).
Dear reader. If you have read this article, it may be for general information purposes or because you fear or believe that you may be suffering from symptoms associated with depression. If the latter is true, I want to remind you that depression is not a personal weakness but a serious medical disorder.
Because depression is a disease, it can not be “willed” or “wished away”. Unfortunately, that is a common misperception by the public and some medical professionals.
Patients with depression often feel terrible. The combination of physical and emotional symptoms may be overwhelming. The tiredness, darkness, and emptiness may seem unbearable. However, depression is a treatable disease. Almost all people who have suffered from depression will tell you that things will get better. And that is true.
And, remember; Never be ashamed of your depression. You wouldn’t if you had a brain tumor, heart attack or leukemia.
Oh, and finally; Don’t try to deal with your depression by yourself. Seek professional help.
For the last few days, my Kindle has been my closest companion.
“What are you reading”? my wife asked. “I’m reading Lore of Nutrition.”
“Ooh, I was sure it was a thriller or one of your crime stories.”
In fact, she was right. Although Lore of Nutrition is a book about nutrition, it reads like a novel. The omertà, the courtroom drama, the hero and the villain (lots of them). Lore of Nutrition has it all.
And, if you’re a cardiologist, the book may read like a Stephen King horror story. However, this time, the horror is real. You’ll just have to hope for a happy ending.
Of course, Lore of Nutrition is not the first book to challenge accepted medical and scientific dogma. But, it rises above most of the others due to its reliance on scientific evidence, its honesty, and bravery. Apart from being a book about nutrition, it is a fascinating story about a man fighting for his credibility and beliefs and his right speak out to the public.
Lore of Nutrition
Lore Of Nutrition is co-authored by two South Africans; sports scientist Professor Tim Noakes and journalist Marika Sboros.
In the preface, Professor Noakes summarizes his background as a doctor and scientist. And what a distinguished career it is. Of course, one might wonder why he has to recapitulate it in such detail. However, when reading on, one learns why he is forced to underscore his credibility.
Tim Noakes has all the characteristics of an opinion maker. His charisma and ability to speak out and explain will make most of us want to listen.
Noakes describes his “Damascene moment”: “It happened after I came face to face with compellingly robust evidence that contradicted everything I believed was true about optimum nutrition to treat and prevent serious diseases, such as obesity, diabetes, and heart disease.”
Noakes challenges two deeply held dogmas: “the role of carbohydrate in nutrition and the diet-heart hypothesis that saturated fat causes heart disease”.
Unfortunately, Noakes learned that the results of his choice to admit his errors and try to correct them would be brutal for himself and his family, “beyond anything that he possibly could have imagined.”
Lore of Nutrition has three main parts.
The first part is about the low-carb revolution in South Africa and Noakes’s first experience with a low-carb, high fat (LCHF) diet. It covers, among other things, the 2015 Low-Carb Summit in Cape Town, the so-called UCT Professor’s letter, The Naudé Review (1), and “The Banting for Babies Tweet” which sparked the now famous Noakes Trial.
The second part covers the trial that was spread over three years, the hearing, the closing arguments and the verdict.
The third part summarizes essential scientific evidence supporting the low-carb, high-fat (LCHF) dietary plan.
Noakes now claims the evidence for the LCHF dietary model is the “best evidence-based model of modern human nutrition. Conversely, the LCHF diet promoted by most health authorities, and religiously taught at all South African medical schools is at best not evidence-based, at worst completely wrong and extremely harmful because it has caused the obesity and type-2 diabetes epidemic.”
Why Does Tim Noakes Have so Many Powerful Enemies?
For an outsider, it is hard to understand why Tim Noakes has so many powerful enemies in his home country and why they believe it’s so important to demolish him. Why do the medical and dietic professional societies in South Africa (HPSCA and ASDA) go to such great lengths to shut him down? It’s just a scientific debate, isn’t it?
Of course, Noakes has expressed opinions that conflict with those taught at the universities. He believes that “the function of universities is to advance knowledge, not to insulate professorial opinions from external scrutiny and thus institutionalize what he calls the power of the anointed.” He writes: “I believe the very reason why universities exist is because we do not (yet) know everything. If we did, we would have no reason to invest so much in costly institutions.”
Noakes also claims the low-fat diet that has been highly promoted for decades is the most likely cause of the epidemic of obesity and type-2 diabetes. He writes: “It is difficult for those who have advocated this fallacy for the past 40 years to suddenly find the courage to acknowledge and apologize for their gross error.”
Or is it Noakes’s methods and how he reaches out to the public that is the problem? Is using social media inappropriate for medical professionals and scientists?
When covering the 2015 Low-Carb summit, Marika Sboros mentions that one of the attendees at the meeting was Jacques Rousseau, a lecturer at the UCT Faculty of Commerce, and an active critic of LCHF and Tim Noakes. Rousseau writes a personal blog called Synapses (2).
Being curious to find out more about a Noakes critic, I took a look at Rousseau’s blog. It is about politics, science, religion, and rationality.
Of course, I was not able to read everything Rousseau has written, but his blog appears to be of high quality, regardless of whether one agrees with him or not.
There are 32 articles on his blog in the series “Noakes”. I wonder if that should that be defined as an obsession?
Interestingly, I found a podcast interview with Rousseau where he says about Noakes: “My criticism has always been about the tone and the approach taken in making the arguments but not about the science and the arguments themselves (3).” So could it be that it is not about what Noakes believes is right or wrong but about how he goes about it?
In Lore of Nutrition, Noakes mentions that the regular headaches he had suffered from disappeared after adopting an LCHF eating plan. He writes: “This is understandable if an allergy to wheat gliadin is a common cause of recurrent headaches, as cardiologist Dr. William Davis proposed in his bestselling book Wheat Belly. Or if a majority of common headaches are caused by gluten sensitivity, as neurologist Dr. David Perlmutter suggested in another New York Times bestseller, Grain Brain.
Being a Noakes admirer, I thought: Please don’t say this. Speculating may be fine, but citing such controversial literature is not very scientific and best avoided in my opinion. I wonder if that’s what Rousseau’s all about.
In a blog post addressing Lore of Nutrition, Rousseau writes: “In short, there’s no vendetta, and if there is a conspiracy, I don’t know of it. Some people (like me) just think Prof. Noakes expresses contingent and as-yet-unproven claims too boldly, in a way that runs ahead of available evidence, whether or not they end up being proven true.”
In another instance, Rousseau writes: “There’s certainly a possibility that he (Noakes) and others are right. As I’ve tried to emphasize, it’s the tone and content of the argument for the conclusion – not the conclusion itself – that I’m addressing (4).”
Tima Noakes, Gary Taubes, and Axel F. Sigurdsson (Reykjavik 2016)
How Will the Cardiologists Respond?
Cardiologists get a fair share of beating in Lore of Nutrition. The critic is specifically aimed at those who do percutaneous coronary interventions (i.e., coronary angioplasty and stenting). I guess it’s fair to mention that I’ve been doing these procedures for more than 20 years myself.
Noakes writes: “Cardiology is responsible for initiating and performing more unnecessary, non-evidence based and costly medical interventions than perhaps any other medical discipline.”
In fact, he may be right. On the other hand, I would like to claim that cardiology is probably the most evidence-based of all medical disciplines.
Noakes goes on by saying that coronary artery bypass surgery “is unnecessary for the vast majority of patients with stable coronary artery disease.” He also says that “in patients with chronic stable coronary artery disease, in the absence of recent myocardial infarction (heart attack) percutaneous coronary intervention does not offer any benefit in terms of death, myocardial infarction, or the need for subsequent revascularization compared with conservative medical treatment.”
Of course, one might be surprised that I don’t disagree with these claims, but I wish Noakes would have mentioned that coronary angioplasty and stenting is an effective treatment strategy for acute coronary syndrome, particularly ST-elevation myocardial infarction (STEMI).
Acute coronary syndrome is a disorder caused by a ruptured atherosclerotic plaque which Noakes elegantly explains in Lore of Nutrition and is the most common reason for a sudden obstruction of blood flow to the heart. There is probably no medical intervention as effective as immediate angioplasty with stenting to open up a recently obstructed coronary artery.
Noakes’s take on statins is fast and furious: “It is of little value to take a drug that might marginally reduce one’s risk of suffering a heart attack or stroke if it increases the risk of dying from something else, without any extension in life expectancy.” Here he is citing the fact that no study has shown benefits of statin treatment in terms of mortality in patients without established cardiovascular disease (primary prevention).
Noakes writes: “Perhaps cardiologists should take heed of the old dictum that “those who live in glass houses should not throw stones”. If you make your money prescribing drugs or performing invasive procedures that have little or no proven benefit and which may cause harm, you need to be very wary of accusing others of doing harm. When it comes to the dietary advice that I promote you should be especially cautious, as there is no published scientific evidence that it causes harm.”
Luckily, not all cardiologists are stone throwers.
The Role of Insulin Resistance
According to recently published evidence, at least 50% of the adult population in the U.S. have insulin resistance, manifested as diabetes or prediabetes (5). Noakes believes this number may be at least 60%. He writes: “Insulin resistance is now certainly the most prevalent medical condition in the world, yet it is not taught or discussed in medical schools.
In the last part of Lore of Nutrition, Noakes writes: “By now it should be clear that all the evidence incriminates carbohydrates and insulin resistance as the key drivers of our current epidemics of ill health.”
Interestingly, he believes that insulin resistance is a relatively benign condition. However, a high carbohydrate diet turns it into a killer. Hence, if you’re insulin resistant, you cannot eat carbohydrates (6).
The Noakes Trial
On 3 February 2014, Twitter user Pippa Leenstra tweeted the following to Tim Noakes and Sally-Ann Creed, his co-author on The Real Meal Evolution:
is LCHF ok for breastfeeding mums? Worried about all the dairy + cauliflower = wind for babies??
Two days later, Noakes tweeted his response to Piippa Leenstra and Sal Creed
Baby doesn’t eat the dairy and cauliflower. Just very healthy high fat breast milk. Key is to ween [sic] baby onto LCHF.
Time Noakes’s twitter response is basically what initiated the HPCSA’s charge against him and the subsequent trial. He was accused of acting in a manner not in accordance with the norms and standards of his profession and for providing unconventional advice on breastfeeding babies on social networks.
Marika Sboros was the only journalist to cover all the hearing sessions of the Noakes trial. She elegantly summarizes the hearing, the closing arguments, and the verdict in Lore of Nutrition.
The Lore of Nutrition is a fascinating book. It contains a story that must be told. And it includes a message that has to be read.
However, don’t let the name fool you. It’s about so much more than nutrition. It’s about science, public health, cardiovascular disease, fatty liver disease, diabetes, the food industry, the diet-heart hypothesis, the pharmaceutical industry, obesity, social media, politics, corruption and academic bullying.
Noakes’s knowledge, enthusiasm, and passion allow him to write in a ruthless manner that is shockingly revealing. Of course, this may be too much and too bold for some of his peers.
Clearly, Noakes can’t be right about everything, but he certainly deserves to be listened to.
Marika Sboros contribution adds to the diversity of the book. Her coverage of the Noakes trial strengthens the storyline and makes the book unique.
It is quite clear that Lore of Nutrition will not help Tim Noakes make peace with his enemies. However, he might make some new friends.
Tremor is defined as an unintentional, rhythmic, oscillatory muscle contraction causing shaking movements of one or more parts of the body. It can affect the hands, head, face, jaw, lips, torso, and legs. Sometimes the voice may be affected as well.
Hand tremor is the most common form.
Tremor is a normal physiologic phenomenon. Most of us see our hands shaking slightly when we hold them out in front of us. Several factors, such as stress, anxiety, lack of sleep, smoking, and caffeine may exaggerate this tremor.
Although tremor is usually not a sign of a severe or life-threatening medical disorder, it can be both embarrassing and disabling to some people and make it harder to perform work and daily life tasks.
Tremor may occur at any age but is most common in middle-aged and older adults. It tends to affect men and women equally.
Tremors are classified as rest or action tremors.
Rest tremor occurs when the affected body part is completely supported against gravity. It may be an arm or a hand that is resting in the patient’s lap. Action tremors, on the other hand, are produced by voluntary muscle contraction. They may occur when writing or lifting a cup of coffee.
Postural tremor is a sub-type of action tremors and occurs when the person maintains a position against gravity such as holding the arms outstretched (1). Postural and action tremors, including exaggerated physiologic tremor and essential tremor, comprise the largest groups.
1. Exaggerated Physiologic Tremor
All normal persons exhibit physiologic tremor. However, it may often be invisible to the naked eye.
Physiological tremor is most evident in the outstretched hands but can be detected in the legs, head, trunk, jaw, and lips.
Enhanced physiologic tremor may be caused by medical conditions such as thyrotoxicosis (overactive thyroid gland), hypoglycemia (low blood sugar), the use of certain drugs, or withdrawal from alcohol, opioids or benzodiazepines. It is usually reversible once the cause is corrected (1).
Beta-blockers may reduce the amplitude of trembling during fine manual work (2). They are often used to treat heart palpitations (3) and tremor due to an overactive thyroid gland.
2. Essential Tremor
Essential tremor is the most common neurologic disorder that causes postural or action tremor. It is the also the most common movement disorder worldwide.
The prevalence increases markedly with age and ranges from 4.1 to 39.2 cases per 1,000 persons, to as high as 50.5 per 1,000 in persons older than 60 years (4). These figures may underestimate the actual prevalence, however, because up to 50 percent of persons with mild essential tremor are unaware of it (5).
More than half of patients with essential tremor have a family history of the disorder (6).
Essential tremor usually develops insidiously and progresses slowly. It often occurs first in the hands and forearms and may be more prominent on one side of the body and increases with goal-directed activity (e.g., drinking from a glass of water or writing).
Essential tremor may also affect the head, voice, jaw, lips, and face. It can include a”yes-yes” or “no-no” motion of the head.
The shaking usually increases with stress, fatigue, and certain medications such as central nervous stimulants. It may also increase with specific voluntary activities such as holding a spoon or a cup.
Interestingly, there is often a degree of voluntary control. Hence, the trembling may be suppressed by performing skilled manual tasks (7).
Although sometimes disabling, essential tremor is in itself a benign disorder and not life-threatening.
Rest, beta blockers, primidone (Mysoline), and alcohol ingestion decrease the trembling.
Primidone and propranolol are the cornerstones of maintenance medical therapy for essential tremor. These medications provide clinical benefit in approximately 50-70% of patients (8).
3. Parkinson’s Disease
Although Parkinson’s disease is probably 20 times less common than essential tremor, about one million Americans suffer from the disease (9).
Tremor is a common symptom of Parkinson’s disease and other Parkinsonian syndromes. However, it is not experienced by all patients with Parkinson’s disease.
The tremor includes shaking in one or both hands at rest. It may also affect the chin, lips, face, and legs. The shaking may initially appear in only one limb or on just one side of the body. It is often made worse by stress, strong emotions, and after exercise.
Sometimes, the trembling only affects the hand or fingers. This type of shaking is often seen in people with Parkinson’s disease and is called a “pill-rolling” tremor because the circular finger and hand movements resemble rolling of small objects or pills in the hand.
Although the trembling of Parkinson’s disease is usually defined as a resting tremor, more than 25 percent of people with Parkinson’s disease also have an associated action tremor (10).
The trembling of Parkinson’s disease differs from essential tremor in three fundamental ways (11):
Essential tremor is more likely to occur during voluntary activity of the hands whereas the trembling of Parkinson’s disease is more prominent at rest.
Parkinson’s disease is usually associated with stooped posture, slow movement, and shuffling gait.
Essential tremor mainly involves the hands, head, and voice. Parkinson’s disease tremors usually start in the hands and arms but also affect the legs, chin, and other parts of your body.
Although Parkinson’s disease can’t be cured, medications may markedly improve symptoms.
4. Intention Tremor (Cerebellar Tremor)
Intention tremor, also known as cerebellar tremor, presents as a unilateral or bilateral shaking, most often caused by stroke, brainstem tumor, or multiple sclerosis (1).
The neurological examination will reveal that finger-to-nose, finger-to-finger, and heel-to-shin testing result in increased shaking as the extremity approaches the target. Other signs include abnormalities of gait, speech, and ocular movements and inability to perform rapid alternating hand movements.
That the shaking typically increases in severity as the hand moves closer to its target, is in contrast to postural and action tremor (like essential tremor), which either remains constant throughout the range of motion or abruptly increase at terminal fixation (12).
Ataxia, a lack of voluntary coordination of muscle movements that includes gait abnormality, is typically associated with cerebellar tremor.
In cerebellar tremor, the finger-to-nose, finger-to-finger, and heel-to-shin testing result in worsening tremor as the extremity approaches the target.
5. Wilson Disease
Wilson disease is a rare autosomal recessive inherited disorder of copper metabolism that is characterized by excessive deposition of copper in the liver, brain, and other tissues (13). Wilson disease is often fatal if not recognized and treated when symptomatic.
Liver dysfunction is the presenting feature in more than half of patients.
The most common presenting neurologic feature is an asymmetric tremor, which is variable in character.
Wilson disease may also be associated with difficulty speaking, excessive salivation, ataxia, clumsiness with the hands, and personality changes.
6. Rubral Tremor
Rubral tremor, also known as Holmes tremor, is a rare symptomatic movement disorder, characterized by a combination of resting, postural, and action tremors.
It is usually caused by lesions involving the brainstem, thalamus, and cerebellum.
The disorder is often difficult to treat. Many medications have been used with varying degrees of success (14).
7. Primary Writing Tremor
Shaking that occurs exclusively while writing, and not during other voluntary motor activities, is referred to as primary writing tremor. Hence, it is a task-specific tremor that predominantly occurs and interferes with handwriting (15).
The cause and pathophysiology of this disorder are still unknown. It has been classified as a focal form of essential tremor and as a tremulous form of writer’s cramp (16).
Botulinum toxin injections and deep brain stimulation may be treatment choices for primary writing tremor (17).
8. Orthostatic Tremor
Orthostatic tremor is a rare disorder, characterized by a rapid trembling limited to the legs and trunk (18). It occurs exclusively while standing.
The disorder is often associated with extreme straining of both legs, fatigue, unsteadiness and a fear of falling. Standing upright for only a short period may be difficult.
The shaking may disappear partially or completely when an affected person is walking or sitting.
There is controversy within the medical literature regarding whether orthostatic tremor is a variant of essential tremor, an exaggerated physiological response to standing still or a distinct clinical entity (19).
The disorder may respond to treatment with clonazepam or gabapentin (Neurontin) (20).
9. Functional Tremor (Psychogenic Tremor)
Functional tremor, also known as psychogenic tremor, is a variable tremor that may decrease or disappear when not under direct observation.
Functional tremor is classified as a functional movement disorder, a term that is applied to disorders that manifest with physical symptoms, specifically abnormal movements (gait disorders, tremor, dystonia, etc.) but which cannot be attributed to any of known underlying organic disorders and which instead is presumed to be due to “psychological factors” (21).
Any body part may be involved, but, remarkably, the fingers are often spared with much of the trembling of the arm occurring at the wrist (12).
A characteristic that suggests functional rather than organic tremors is abrupt onset with immediate maximal severity, often precipitated by trivial emotional or physical trauma (22).
Patients with functional tremor often have more than one movement disorder, which can be a helpful clue to the diagnosis.
10. Drug-Induced Tremors
Several medications can cause or exacerbate tremor (1).
“Fatigue is here, in my body, in my legs and eyes. That is what gets you in the end. Faith is only a word, embroidered.”
― Margaret Atwood, The Handmaid’s Tale.
Fatigue or tiredness is a common medical complaint that may seriously affect people’s quality of life. However, despite many possible underlying causes, a specific medical disorder is seldom revealed. On the other hand, mood and anxiety disorders are commonly associated with fatigue.
Fatigue is regarded as a nonspecific symptom as it is not typically associated with a particular disease. It is one of the most common complaints reported to medical care providers.
Contrary to many other medical symptoms, fatigue is an entirely normal phenomenon in particular situations. We all become tired, but it usually gets better by rest or sleep. However, chronic fatigue as a medical symptom is typically persistent and not relieved by rest. The words lethargy and malaise are sometimes used to describe this condition.
Approximately 6-7 percent of the population experiences fatigue at any given time, and 24 percent of people will suffer from fatigue at some time during their course of life (1). Most studies show that fatigue is more prevalent in women than in men.
One study showed that 24 percent of primary care patients consider fatigue to be a significant problem (2). It is estimated that fatigue will result in approximately seven million office visits per year in the primary care setting in the United States (3). However, despite the frequency of medical utilization, one study found that only 10 percent of patients in an internal medicine clinic were found to have a medical cause for their fatigue (4).
Fatigue caused by an underlying medical condition such as a viral infection, anemia or hypothyroidism will usually clear up when the underlying condition is treated. That’s different from chronic fatigue which is persistent and is usually not be explained by a specific underlying medical condition. Fatigue that is present for more than six months is regarded as chronic.
An underlying medical or psychiatric condition can explain chronic fatigue in approximately two-thirds of the patients (5). The three major underlying psychiatric illnesses are depression, panic disorder, and somatization disorder (6).
Chronic fatigue syndrome (CFS), also known as systemic exertion intolerance disease (SEID) is regarded as a separate disease entity. Studies have indicated that approximately 15 percent of patients with chronic fatigue suffer from CFS (7).
Apart from affecting the quality of life, fatigue may negatively impact family life, social relationships, and performance at work. Consequently, it should be regarded as an essential public health issue. However, as so often with nonspecific symptoms that cannot easily be explained or fixed with a prescription or another simple measure, fatigue, as long as it is not caused by a severe medical disorder, often tends to be stashed away.
The Definition of Fatigue
Fatigue is a generalized perception of weakness or feeling worn out, drained or depleted.
Sometimes a distinction is made between physical and mental fatigue. However, in many cases, these occur together.
Physical fatigue is a reduced capacity to maintain physical activity or an inability to initiate physical tasks. However, mental fatigue is characterized by difficulties with concentration, memory, and emotional stability (8).
It is important to differentiate between daytime sleepiness and fatigue. Sleepiness is the inability to remain fully awake or alert during the day whereas fatigue is a subjective lack of physical or mental energy interfering with daily activities. Daytime sleepiness is a key feature of obstructive sleep apnea (9).
Fatigue should be distinguished from dyspnea and muscle weakness. Dyspnea describes a sense of breathing discomfort or difficulty in breathing. It is often expressed as feeling out of breath or suffering from breathlessness (10). Muscle weakness implies lack of muscle strength and is associated with several neurological and skeletal muscle disorders. Of course, patients with dyspnea and muscle weakness may also complain of fatigue.
The duration of fatigue can be recent (less than one month), prolonged (more than one month), or chronic (over six months) (11).
1. Chronic Fatigue Syndrome (CFS)
Chronic fatigue syndrome (CFS) is a disorder characterized by chronic fatigue, has no apparent cause, and is accompanied by cognitive difficulties (12). Examples of cognitive problems include verbal dyslexia and difficulties with short-term memory. It is estimated that between 836.000 and 2.5 million individuals are affected by CFS in the United States (13).
CFS has also been named systemic exertion intolerance disease (SEID) to better reflect the condition’s hallmark which is post-exertional malaise. Post-exertional malaise describes a massive energy crash after a relatively minor exertion. Generally, if this condition is accompanied by cognitive difficulties, it is referred to as CFS.
The cause of CFS is unknown, but it is believed to be an infectious disease with immunologic manifestations. There is often a history of an antecedent infection that precipitated the prolonged state of fatigue following the initial illness. Some have suggested that the infectious agent responsible for CFS is Chlamydia pneumoniae.
A recent study suggested that a blockage of a key metabolic enzyme could explain the profound lack of energy and other symptoms experienced by patients with CFS (14). The study suggests that patients with CFS have a reduction of amino acids that fuel oxidative metabolism, pointing to functional impairment of pyruvate dehydrogenase (PDH), a key enzyme for the conversion of carbohydrates to energy. Hence, the cells might switch to consumption of alternative fuels, causing a sudden shortage of energy in the muscles and a buildup of lactate, experienced by patients as a burning sensation in their muscles after minor exertion.
There is no specific diagnostic test for CFS. The diagnosis is based on clinical criteria, which are further supported by certain nonspecific tests. The absence of cognitive dysfunction should exclude CFS as a potential diagnosis.
In 2015, the following diagnostic criteria were proposed for CFS by the Institute of Medicine (IOM)(15).
Ongoing (>6 months) substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest
Post-exertional malaise (often described by patients as a “crash” or “collapse” after even minor physical or mental exertion)
At least one of the two following manifestations is also required
In their 2015 report, the IOM wrote: “However, CSF is poorly accepted and poorly understood, and the characteristics necessary to make the diagnosis are contested. Patients concern are often met with dismay and skepticism, if not outright dismissal. Clinicians, in turn, are confronted by competing definitions, which were usually developed for research and are quite complex and difficult to implement in busy clinical practice. Patients who are fortunate enough and persistent enough to receive a correct diagnosis frequently report long delays before their disorder was identified. It is almost certainly the case that the majority of affected patients are never diagnosed. This is unfortunate because effective symptom management is often available, whereas the wrong interventions can make symptoms worse (15).”
2. Idiopathic Chronic Fatigue
The first step in the evaluation of patients with chronic fatigue is to screen for an underlying medical or psychiatric illness. If no such disorders can be found and the patient does not fulfill the criteria for the chronic fatigue syndrome (CFS), he/she may be considered to have idiopathic chronic fatigue. The word ‘idiopathic’ reflects an unknown underlying cause.
Disability rates and need for healthcare is similar for patients with idiopathic chronic fatigue and CFS (16).
Fibromyalgia is a chronic pain syndrome characterized by widespread nonarticular pain, stiffness, and fatigue.
Cognitive complaints, known as fibrofog, are present in 90 percent of patients (17).
For years, fibromyalgia has been regarded as a controversial condition. In most cases, no abnormalities are found on physical examination other than tenderness in certain areas affected. Laboratory and radiographic findings are normal. Thus, the role of organic illness has been questioned, and fibromyalgia has often been considered to be of psychogenic or psychosomatic origin (18).
Modern brain imaging has provided new insights into the mechanisms involved in fibromyalgia. Recent research suggests that fibromyalgia is a disorder of pain regulation, linking fibromyalgia to changes in brain activity (19).
Fatigue is a universal symptom of fibromyalgia. It is often most marked when arising from sleep in the morning. A typical quote is “No matter how much sleep I get, it feels like a truck ran me over in the morning (20).” Minor activities often seem to aggravate the fatigue.
Fatigue Caused by Underlying Medical Conditions
Fatigue may be caused by several underlying medical conditions. However, among patients with chronic fatigue, only a small proportion (approximately 10%) will have an underlying medical disorder as the primary cause of their symptoms.
Laboratory studies should include complete blood count, chemistry screen (electrolytes, glucose, renal and liver function test), thyroid stimulating hormone (TSH), and creatine kinase if muscle pain or weakness is present. Screening for occult hepatitis C viral infection may sometimes be appropriate as well as screening for HIV. These tests should reveal most common medical disorders potentially causing fatigue.
Anemia is a medical condition in which the red blood cell count is below normal. Patients with anemia typically experience fatigue and loss of energy.
Iron deficiency anemia is the most common type of anemia worldwide. It is commonly caused by blood loss such as from heavy menstrual bleeding or bleedings from ulcers or tumors in the gastrointestinal tract.
Anemia may be caused by a deficiency of B-12 and folate.
Anemia may also be caused by diseases of the bone marrow such as leukemia and myelofibrosis
Many chronic diseases such as cancer, rheumatoid arthritis, and kidney disease may cause anemia.
Hypothyroidism is a condition in which the thyroid gland doesn’t produce enough of the thyroid hormones known as T3 and T4.
Fatigue is one of the leading symptoms of hypothyroidism. Other symptoms include increased sensitivity to cold, constipation, dry skin, hoarseness, muscle weakness, muscle aches, thinning hair, depression and impaired memory.
The pituitary gland responds to diminished levels of T3 and T4 by increasing the secretion of thyroid stimulating hormone (TSH). Hypothyroidism is usually detected by elevated blood levels of TSH.
Treatment of hypothyroidism with synthetic thyroid hormone is usually simple, safe and effective.
6. Diabetes Mellitus
Many people with diabetes describe themselves as feeling tired, lethargic or fatigued at times.
Fatigue may be caused by an imbalance in blood sugar levels. It may be present when blood sugar is high and when it is low.
People with diabetes may also experience chronic fatigue that is not always related to their blood sugar levels. This phenomenon is known as diabetes fatigue.
7. Other Endocrine Disorders
Hypothyroidism and diabetes mellitus are examples of endocrine disorders known to cause fatigue.
Several other endocrine and metabolic disorders are associated with tiredness (21). Examples are hypogonadism (22), hyperparathyroidism with associated hypercalcemia, adrenal insufficiency (adrenal fatigue), apathetic hyperthyroidism, growth hormone deficiency, and glucocorticoid resistance (23).
8. Chronic Infections
Several chronic infections may cause fatigue. Examples are endocarditis (an infection of the heart valves), tuberculosis, mononucleosis, hepatitis, parasitic disease, HIV infection, and cytomegalovirus.
Additional laboratory tests may be necessary to reveal these disorders.
9. Autoimmune Disorders
Sometimes, in response to an unknown trigger, the immune system may begin producing antibodies that attack the body’s own tissues. This may lead to a chronic inflammatory response and is characteristic for most autoimmune disorders.
Examples of autoimmune disorders are rheumatoid arthritis, systemic lupus erythematosus (lupus, SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus, Guillan-Barre syndrome, psoriasis, Graves´disease, Hashimoto’s thyroiditis, and myasthenia gravis.
Fatigue is a major component of autoimmune disorders. Tiredness described as “profound,” “debilitating,” and “preventing them from doing the simplest everyday tasks,” is a major issue for many patients, impacting nearly every aspect of their lives (24).
Chronic fatigue is prevalent in people with cancer and can often be the most troubling symptom. This type of tiredness is sometimes called cancer-related fatigue or cancer fatigue.
Fatigue is now overshadowing pain and nausea/vomiting as one of the most feared symptoms of cancer and cancer treatment (25).
Cancer-related fatigue may be caused by the disease itself. Sometimes, tiredness is the first symptom of cancer. However, people with advanced cancer are more likely to have fatigue than people in the earlier stages.
Cancer-related fatigue may also be related to other factors such as anemia, anxiety, depression, and side effects of treatment.
11. Sleep Disorders
Daytime sleepiness is a key feature of obstructive sleep apnea (9).
However, sleepiness and fatigue are not the same. Sleepiness is the inability to remain fully awake or alert during the day while fatigue is a subjective lack of physical or mental energy interfering with daily activities.
Nonetheless, people with sleepiness due to obstructive sleep apnea use terms like fatigue, tiredness, and low energy to describe their symptoms.
12. Central Nervous System Disease
Several neurological conditions may be associated with fatigue. For example, tiredness is often a prominent symptom in patients with stroke, multiple sclerosis, and Parkinson’s disease.
It is important to look for symptoms or signs of central nervous system disease when evaluating patients with chronic fatigue.
13. Neuromuscular Disease
Fatigue may be present in several neuromuscular disorders such as Amyotrophic Lateral Sclerosis (ALS), Post-Polio Syndrome (PPS), Guillain-Barre Syndrome, Immune Neuropathy, Charcot-Marie-Tooth Disease, Myasthenia Gravis (MG), Metabolic Myopathy, Mitochondrial Myopathy, Muscular Dystrophy, Facioscapulohumeral Dystrophy, Myotonic Dystrophy (26).
Hence, it is important to look for muscle weakness and signs of neurological disease when evaluating patients complaining of tiredness.
14. Gastrointestinal Disorders
Several gastrointestinal disorders may be associated with fatigue. Examples are peptic ulcer disease, gastroenteritis, inflammatory bowel disease (IBD), cancer, and irritable bowel syndrome (27).
However, patients with gastrointestinal disorders will usually have other complaints as well, such as abdominal pain, nausea, vomiting, constipation, or diarrhea.
15. Cardiovascular Disorders
Tiredness may be a sign of underlying heart disease. Therefore it is important to look for symptoms such as chest pain (28) and shortness of breath (29).
The most common heart attack symptom in men and women is chest pain or discomfort. However, only half of women who have heart attacks have chest pain.Women are more likely than men to report back or neck pain, indigestion, heartburn, nausea, vomiting, extreme fatigue, or problems breathing (30).
Patients with chronic heart failure often have fatigue, diminished exercise tolerance, and fluid retention.
Heart failure occurs when the heart muscle is weakened and cannot pump enough blood to meet the body’s needs for blood and oxygen. In some cases, the pumping capacity of the heart muscle is preserved, but left ventricle is stiff with decreased compliance and impaired relaxation, which leads to increased filling pressure in the left ventricle.
Heart failure is caused by an underlying heart disease that has caused damage to the heart muscle and/or an increased stiffness of the left ventricle. Coronary heart disease, hypertension, valvular disorders and dilated cardiomyopathy are the most common causes of heart failure.
Heart failure affects between 1–2% of the general United States population and occurs in 10% of those over 65 years old (31).
16. Chronic Obstructive Pulmonary Disease (COPD)
Chronic obstructive pulmonary disease (COPD) refers to a group of conditions that cause airflow blockage leading to shortness of breath, cough, mucus (sputum) production and wheezing. It includes emphysema, chronic bronchitis, and in some cases asthma.
Tobacco smoke is the leading cause of the development and progression of COPD in the United States (32). Genetic factors, exposure to air pollutants, and respiratory infections also play a role.
COPD was the third leading cause of death in the United States in 2014 (33).
Emphysema and chronic bronchitis are the two most common conditions that contribute to COPD.
Although shortness of breath is the most common symptom of COPD, many patients complain of fatigue (34).
Psychologic Causes of Fatigue
Psychiatric illness is present in 60-80 percent of patients with chronic fatigue (35,36).
17. Anxiety and Depression
Anxiety and depression are common causes of fatigue. The tiredness is usually persistent but may vary in intensity.
Up to three-quarters of patients with chronic fatigue also have mood or anxiety disorders. It has even been suggested that chronic fatigue is an atypical form (forme fruste) of anxiety or depressive states (37). In other words, chronic fatigue might be just another form of anxiety or depression.
Some people with depression experience total lack of energy sometimes called ‘anergia’.
There is evidence to suggest that depression may predispose individuals to subsequent fatigue (38). On the other hand, fatigue and depression have been found to predict and influence each other in time. Their association could partly be due to some common risk factors that give rise to both. For some, fatigue will come first; for others, depression will come first, but for most, it will probably be unclear (39).
18. Somatization Disorder
A person with somatization disorder is preoccupied with numerous “somatic” (physical) symptoms. The symptoms often cause significant distress and interfere with daily life. However, the person’s complaints cannot be explained by an underlying medical disorder.
Patients with somatization disorders often complain of pain or fatigue. Symptoms are often of gastrointestinal nature, such as nausea, bloating, and diarrhea. Erectile dysfunction is a common complaint in men. Women may experience menstrual irregularities. Neurological symptoms such as impaired coordination, difficulty swallowing, loss of touch or pain sensation, and double vision are often present.
It is important to understand that the patient is not faking. His/her complaints are real.
Somatization disorder usually begins before the age of 30 and is more common in women than men.
To qualify for the diagnosis of somatization disorder, somatic complaints must be severe enough to interfere significantly with a person’s ability to perform important activities, such as work, school or family, and social responsibilities, or lead the person experiencing the symptoms to seek medical treatment (40)
Patients with somatization disorder often undergo numerous medical tests..