Predicting whether a child will outgrow asthma has important implications for patients, parents and doctors. Past studies have estimated between 15% to 64% of patients with childhood asthma go into remission by early adulthood. In those studies asthma remission rates have been noted to vary widely by population, and remission has been associated with less allergenic sensitization, milder initial asthma severity and male sex. Asthma remission commonly occurs by the ages of 14 to 21 years.
In a recent study published in The Journal of Allergy and Clinical Immunology, researchers determined which baseline characteristics could determine which children have a higher likelihood to outgrow asthma by adulthood.
The main conclusions from the study determined:
26% of patients with mild to moderate asthma had clinical remission of disease by early adulthood.
Baseline airflow obstruction measured by spirometry (pulmonary function test) was the greatest predictor of asthma remission. More than half the boys and 2/3 of the girls who performed greater than 90% on spirometry (using FEV1 and FVC ratio), were in remission by adulthood.
Decreased airway responsiveness and lower serum eosinophil counts also were predictive of whether or not one will outgrow asthma.
Lung function measurements and serum eosinophil counts obtained in early childhood predict asthma remission in early adulthood. Pulmonary function testing (spirometry) should be performed in all patients with childhood asthma for clinical outcomes.
This study followed 879 children with mild to moderate asthma for an average of 12 years until early adulthood. Using the 3 parameters, lung spirometry, airway responsiveness (from methacholine challenge) and serum eosinophil counts (greater or less than 500), remission rates can be predicted.
Conclusions of the study showed a considerable minority of patients with persistent childhood asthma will have disease remission by adulthood. So it would be difficult to tell parents their child will outgrow asthma unless their spirometry results are over the 90% range and they have low eosinophil counts on lab work.
Uncontrolled asthma is a significant problem worldwide. Many patients can use controller medication that have been around for decades. A major problem though is nonadherence to regular use of inhaled corticosteroids and long acting beta agonists. Once medication adherence has been undergone and patients still have continued asthma exacerbations, one of the asthma biologic medications can be considered. The costs of asthma biologics are an important factor to consider for patients. The wholesale acquisition cost of 1 year of treatment excluding administration costs are below:
Xolair $39,048 (Xolair’s dose can vary widely depending on the patients weight and IgE level, the higher the dose and weight, more Xolair would be needed, necessitating higher costs). XOLAIR Dosing Tool for Allergic Asthma
Nucala $37,293 (Nucala dosing is 100mg every 4 weeks)
Cinqair $31,637 (Cinqair is dosed by weight, 3mg/kg every 4 weeks by an IV infusion, so the dose can vary widely depending on the weight).
Fasenra $30,889 (Fasenra is given 1 time a month for the first 3 months at 30mg, then every 8 weeks after, although the maintenance dose is given every other month, the cost is relatively the same as the other biologics).
Dupixent $38,110 (Dupixent has a loading dose of 600mg then it is given at 300mg every 2 weeks, the injections can be self-administered at home).
As you can see, the costs of asthma biologic medications are extremely high. There has been studies debating the cost effectiveness of these medications, and there will be further studies about it. A recent study published in The Annals of Allergy, Asthma and Immunology concluded the costs of biologic medications need to be reduced by approximately 60% to meet cost-effectiveness. Another factor is the duration of treatment, as of now manufacturers recommend continued treatment of the medications.
In terms of effectiveness, all currently approved biologics have relatively comparable efficacy when compared to placebo. Head to head studies are currently lacking. In another blog post we did explore some head to head data.
Mast cell activation syndrome (MCAS) is a rare condition defined by a severe systemic reaction to mast cell derived mediators. Mast cells are effector cells of the immune system. These cells produce a variety of proinflammatory mediators and participate in a number of different pathological conditions. In patients the risk of developing severe anaphylactic (hypersensitivity) events is high.
Mast cell activation is found in many pathological conditions, from drug reactions, food allergies and those who suffer from systemic mastocytosis. When the symptoms are severe and recurrent and meet criteria confirming mast cell involvement, the diagnosis of mast cell activation syndrome (MCAS) can be established.
Common symptoms seen are itching, headache, flushing, abdominal pain, fast heart rate, but they are not specific for mast cell activation. An increasing number of patients are referred because they believe or had been informed that they are suffering from mast cell activation syndrome. Many of these patients do not fulfill the criteria of MCAS. This in turn leads to more frustration in both patients and caregivers as well as the inappropriate use of health care resources.
There are consensus criteria that are widely accepted for the diagnosis of mast cell activation syndrome.
the episodic (recurrent) occurrence of typical, systemic symptoms that are produced by mast cell mediators and involves at least 2 organ systems.
an increase in mast cell mediators, preferably serum tryptase by at least 20% over the individual tryptase level plus 2ng/ml, within 3-4 hours after the reaction.
a substantial (documented) response to drugs that block histamine or suppress mast cell activation.
There may be a number of different clinical conditions and disorders that can mimic MCAS. Here is a list of them:
Mast cell activation syndrome can be further classified into primary (clonal), secondary and idiopathic.
Most patients with mast cell activation syndrome suffer from recurrent episodes of severe hypotension (anaphylaxis). If this is not the case, MCAS is a less likely diagnosis. Patients with multiple chemical and environmental intolerances or multiple food intolerances should not be diagnosed as MCAS. 2 or more organs systems need to be involved. When the tryptase level increases substantially during an attack, the reaction can be regarded as mast cell related. Patients with MCAS may suffer from an IgE-dependent allergy and/or underlying mastocytosis.
Advice for affected individuals-many patients are being told that their symptoms are due to mast cell activation or MCAS. Others believe that they could suffer from MCAS when they undergo self-evaluation from questionnaires on the internet, however many do not fulfill the criteria. An answer of “yes” to the majority of following questions make the likelihood of MCAS high.
Did my symptoms repeatedly occur in the form of severe attacks requiring immediate intervention or hospitalization?
Did my symptoms lead to an anaphylactic shock?
Was my serum tryptase level measured before, during and after an attack?
Is my serum tryptase increased during an attack?
Did my symptoms improve with antihistamines?
Did the attacks less with steroids or antihistamines?
Do I have an IgE-dependent allergy?
Did my attacks resolve/decrease with Xolair (omalizumab)?
In conclusion, diagnostic criteria has been established and should be used for mast cell activation syndrome. A key diagnostic marker is the event-related increase in mast cell tryptase over the individual’s baseline. When it exceeds 20% from baseline plus 2 ng/ml the diagnosis of MCAS is very likely. Other conditions need to be considered when MCAS criteria are not met. This is important because some are serious and life threatening instead of misdiagnosing mast cell activation syndrome.
Cold hives (or urticaria), is a subtype of physical hives that is characterized by the development of hives and swelling in response to cold exposure and rewarming of the skin. It is related to the histamine release of mast cells. Several studies have shown that it is related to IgE and an unknown skin autoallergen that becomes accessible with cold stimulation.
The way it can be diagnosed is with cold provocation tests through application of a cold stimulus (ice cubes, cool packs, cold water baths) to the forearm for 5 minutes and the arms are assessed after 10 minutes. Positive reactions are indicated by the development of hives within minutes of rewarming the skin.
Cold exposure can also lead to a potentially serious and fatal reaction in specific circumstances (jumping into a cold body of water) can lead to anaphylaxis. Some patients may need to carry an injectable epinephrine for those at risk. Reactions can also occur with cold weather, snow, air conditioning, walking down an cold aisle in a supermarket, holding a cold drink or grabbing a cold surface or eating something cold (ice cream).
Besides avoiding the cold, other treatments are available. Non sedating second generation antihistamines and Xolair (omalizumab) are being used to treat cold hives.
Antihistamines such as Clarinex (desloratadine), Xyzal (levocetirizine), Zyrtec (cetirizine), Allegra (fexofenadine), are just some of the few that are used to treat and prevent hives in patients with cold urticaria. Older antihistamines work well too, but they can cause sedation in higher dosages (cyproheptadine, doxepin and hydroxyzine). Cyproheptadine 4mg given 3 times a day, has been shown to completely suppress hive formations in a landmark study of cold urticaria, but other non-sedating antihistamines seem to work just as well.
The side effects of using a non-sedating H1 antihistamine in higher dosages can be; sleepiness, dizziness, headaches, stomach pain and fatigue. Although they are generally well tolerated, most side effects are seen if a 1st generation (sedating) is used.
The biggest takeaway for the treatment of cold hives is that non-sedating antihistamines are effective in the treatment of cold hives in higher than standard doses (up to 4-fold), and updosing does not increase side effects. For treatment resistant patients, Xolair monthly is also effective, although this is an off-label use.
Asthma is one of the most common chronic diseases that can complicate pregnancy. It can put women at increased risk of pregnancy outcomes.
Postpartum depression is a nonpsychotic depressive episode that begins after delivery, most occur 1 to 3 months after delivery, but its onset may occur as late as 12 months after delivery. It is one of the most common psychological problems in women. Postpartum depression is associated with impaired cognitive and emotional development of the infant and the long term consequences can be substantial.
A recent study published in The Journal of Allergy and Clinical Immunology: In Practice, titled Risk of Postpartum Depression Among Women with Asthma, compared the risk of postpartum depression between women with asthma and those without asthma during pregnancy.
The results found that women with asthma were 58% more likely to experience postpartum depression within 1 year after delivery than women without asthma during pregnancy.
Several hypotheses were made to help explain the link between asthma and depression.
A link with an early exposure to stress leading to a steroid resistance, which causes disturbances to the immune system through several pathways. These deregulations induce inflammation, which has been associated with both asthma and depression.
The second hypothesis involves proinflammatory circulating cytokines. These cytokines disturb the hypothalmic-pituitary-adrenal system, affecting the immune system. They also regulate inflammatory responses through pathways that may be involved in asthma and depression.
It is possible that new mothers with asthma may have experienced increased feelings of anxiety and helplessness due to the potential negative consequences of having a chronic, life-threatening disease. It is also possible that mothers with asthma may have experienced greater stress during the post-partum period due to the added strain of managing a chronic disease as well as looking after the infant.
Others have described the link between depression and autoimmune disorders, with inflammation being associated with behavioral changes such as depression.
A close monitoring of signs of depression for pregnant women with asthma is indicated, allowing prompt and efficient interventions if needed.
The gut microbiome (bacteria) can play a strong role in food allergies. Food allergy is a clinical and public health problem that affects up to 10% of the US population. It is defined as an adverse health effect arising from a specific immune response that occurs on exposure to a food. IgE food mediated allergy is a relative immediate response that affects the skin, respiratory, gastrointestinal and cardiac symptoms. The cause of food allergy involves deviation from a default state of immune tolerance that is likely driven by antigen exposure, gut bacteria and their interactions.
The gut bacteria outnumber human cells and genes, motivating interest in how their dysregulation may influence host immunologic development and risk for allergic disorders. Growing evidence supports a potential role for the gut microbiome in the pathogenesis and course of food allergy. Future investigations will direct areas where interventions can take place in the prevention of food allergies.
There is growing evidence that supports a role for the gut microbiome (The entire habitat, including the micorbiota, their genomes (genes) and the surrounding site-specific conditions). Gut dysbiosis (descriptive for imbalance in a microbiome, such as lack of homeostasis in microbial composition or functions) may precede the development of food allergy, and the timing of such dysbiosis is critical.
Gut microbiota (the assemblage of all microorganisms present in a defined site or niche) with individual food allergies may be distinct.
Mouse models suggest that gut microbiota affect food allergy susceptibility by modulating type 2 immunity, influencing immune maturation and tolerance, regulating basophil populations and promoting intestinal barrier function.
There are potential modalities for gut microbiome manipulation.
Synbiotics (products that contain both prebiotics and probiotics) Bifidobacterium breve M-16v
A new sublingual tree tablet is currently being developed for the treatment of tree pollen induced allergic rhinoconjunctivitis. Allergic rhinitis is estimated to affect 500 million individuals worldwide and is considered a global health problem. It leads to lower school and work performance. Allergic rhinitis is also a risk factor for asthma development.
Currently allergy shots to trees (subcutaneous immunotherapy) leads to the desensitization of tree pollen. There are no sublingual tree tablets available. There are however sublingual tablets for dust, grass and ragweed currently available.
Exposure to three pollen is prominent across Europe and North America. Tree pollen induced allergic rhinitis is commonly caused by allergens from birch, alder, hornbeam, hazel and oak. Birch pollen sensitization is estimated to be 24% in Europe and 16% in the U.S. The only long term strategy for immunomodulation are allergy shots and sublingual tablets/drops.
The sublingual tree tablet is being developed by ALK-Abello to treat allergies from the birch family. In this phase 3 clinical trial, the aim was to demonstrate the efficacy and safety of the sublingual tree tablet compared to placebo in adolescents and adults with birch pollen induced allergic rhinoconjunctivitis not only during the birch pollen season but also during the tree pollen season, comprising hazel, alder and birch.
Conclusions of the study showed:
The sublingual tree tablet provided clinically relevant and statistically significant improvements in the combined allergic rhinoconjunctivitis symptom and medication score during the birch season and during the entire tree pollen season comprising hazel, alder and birch.
Improvement manifested through both reduced symptoms and reduced medication use.
Treatment was well tolerated with no major safety concerns.
The sublingual tree pollen tablet may be an attractive option for those who are predominantly allergic to birch pollen. A potential issue though may be for the patients who are not only allergic to birch pollen, but other tree pollens that are not related to birch. Unlike grass pollen, many tree pollens do not cross react with each other and patients need to be desensitized to each one individually. The allergy doctor will need to decide whether a patient is the right candidate to start allergy shots for different trees or to just use a sublingual tree tablet for the birch tree only.
There is no current cost or name for the sublingual tree tablet. But like the other sublingual tablets mentioned above, the manufacturer will most likely have coupons and/or rebates for those who are prescribed it. Stay tuned for more information.
There have not been many studies to see whether someone can outgrow seafood allergy unlike peanut allergy where 20% is considered the norm. Can you outgrow peanut allergy?
Seafood allergy includes allergy to either fish or shellfish although the main allergenic proteins differ between these groups. Worldwide prevalence of allergy to fish is reported to be as high as 1.5% for adults and 7% for children, whereas shellfish allergy is reported to affect up to 2% of adults and 5.5% of children.
In the United States, 0.5% of adults and 0.2% of children reported fish allergy and shellfish allergy was reported in 2.5% versus 0.5% respectively. Seafood is therefor a relatively prevalent group of allergens and together with peanut and tree nut accounts for the most severe cases of food-induced anaphylaxis.
A recent study in Canada published in The Journal of Allergy and Clinical Immunology In Practice, studied the rate to outgrow seafood allergy.
Participants were considered allergic to fish/shellfish if they met at least 1 of the following criteria.
Convincing history and positive skin test result. A convincing history referred to at least 2 mild signs and/or symptoms or 1 moderate or severe sign and/or symptom that was likely IgE-mediated and occurred with 120 minutes of seafood ingestion, skin contact or inhalation. Mild signs/symptoms included itching, hives, flushing, itchy throat or rhinoconjunctivitis; moderate signs/symptoms included swelling, stridor, coughing, abdominal pain, difficulty breathing, voice changes, nausea, vomiting or diarrhea; severe symptoms included wheezing, cyanosis and circulatory collapse
Specific IgE levels in the blood for fish of at least 20 kU/L
Positive oral challenge
Participants reported the most common fish and shellfish allergy culprits were salmon (18.4%) and shrimp (50%) respectively.
The resolution rate for fish was only 0.6% and 0.8% for shellfish, per person-year.
Given these results, it is very unlikely a patient will outgrow seafood allergy, whether it be fish or shellfish. Given these low rates, it would not be part of routine clinical practice to challenge these patients especially if their blood allergy IgE is 20kU/L or higher.
Ryaltris is a new nasal spray (formerly GSP301) that is being investigated by Glenmark Pharmaceuticals for the treatment of seasonal allergic rhinitis in patients 12 years and older. Ryaltris consists of 2 drugs, the first one is olopatadine hydrochloride, a nasal antihistamine, which is the medication used in Patanase nasal spray. The second medication is a steroid, mometasone furoate monohydrate, which is the active ingredient for Nasonex nasal spray.
Using both of these medications together would make it easier for patients than using 2 separate nasal sprays. Nasal steroids and nasal antihistamines have both been shown to be effective in the treatment of allergic rhinitis. Approximately 50% of patients with allergic rhinitis need more than 1 medication and Ryaltris would meet the need of many of those patients. The gold standard to treat allergic rhintis, is a nasal steroid spray.
If the type of ingredients of Ryaltris sounds familiar, it is. Dymista nasal spray is also a combination of a nasal steroid (fluticasone propionate 50 mcg) and an antihistamine (azelestine hydrochloride 137 mcg). Many patients have enjoyed the convenience of using 1 nasal spray over 2, but many insurance companies balked at paying a higher price for Dymista. Insurances have required prior authorizations or they were excluded from drug formularies, making it difficult for patients to obtain. Ryaltris may have the same difficulties moving forward.
Allergic rhinitis is an inflammatory disease that affects 16 million adults and 5.5 million children in the United States. It can affect quality of life, decrease work and school productivity, disturb sleep, cause fatigue, irritability and depression.
An intranasal antihistamine can give fast-acting relief and an intranasal corticosteroid can be effective long term. Using a single device combination treatment can improve treatment adherence. Olopatadine when applied intranasally reduces itchy/runny nose and sneezing. Mometasone reduces nasal itching and congestion, sneezing and runny nose by inhibiting the release of inflammatory mediators and it has a well documented safety profile with minimal systemic effects.
A recent study looked at Ryaltris titled “Effect of olopatadine-mometasone combination nasal spray on seasonal allergic rhinitis symptoms in an environmental exposure chamber study” evaluated the efficacy of this new spray. The conclusion found that in an environmental exposure chamber model, twice-daily and once daily Ryaltris treatments were well tolerated and provided statistically significant and clinically meaningful allergic rhinitis symptom improvement vs placebo.
Stay tuned for the release of Ryaltris, it is not known at the present time what the cost will be and whether or not medical insurance will cover it. Here is the press release from Glenmark Pharmaceuticals regarding Ryaltris.
Tree nut allergy is usually lifelong and together with peanut allergy are the most common cause of food induced anaphylaxis. There is not as much data compared to peanut allergy.
Children with peanut allergy are thought to be at increased risk of tree nut allergies, with around 30% of pediatric patients presenting with peanut allergy reported to have allergies to tree nuts.
In a recent study published in the Journal of Allergy and Clinical Immunology, researchers sought to estimate the population prevalence of tree nut allergy during the first 6 years of life.
Tree nut allergy affected 3.3% of 6 year olds, with cashew being the most common, followed by pistachio, hazelnut, walnut and almond. Of note, peanut is not a tree nut, but a legume.
At 1 year of age, 41% of those with egg or peanut allergy were already sensitized to 1 or more tree nuts. At age 6 years, almost half developed tree nut allergy.
The authors who were based in Australia, noted high regional variation of the type of nut allergy. In Europe, studies report hazelnut as the most common nut allergy. This is largely based on the high rate of birch pollen allergy and its cross reactivity to hazelnut. In the UK, Brazil nut was reported as the most common tree nut allergy. In the U.S., walnut and cashew were reported as the most common.
Conclusion: Tree nut allergy is uncommon in the first year of life, likely because of limited tree nut consumption. At age 6 years, its prevalence is similar to peanut allergy prevalence. More than a third of children with both peanut and egg allergy in infancy have tree nut allergy at 6 years.
A big breakthrough in peanut allergy has been the study which showed the early introduction of it decreased the development of allergy.
If the data from the peanut study is inferred, the early introduction of tree nuts may also decrease allergy. Tree nuts are a choking hazard to children, so it may be more advisable to given in the form of cashew or almond butter for example. More understanding in how to prevent tree nut allergy should be an urgent priority for future research.