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Diagnosis of asthma.
Early diagnosis allows prompt treatment and better outcomes. The diagnosis of asthma is based on an appropriate clinical history, together with the demonstration of variable and/or reversible airflow limitation on lung function testing.
As defined by the Global Initiative for Asthma (GINA) guidelines, the patient should complain of one or more of symptoms of episodic wheeze, chest tightness, shortness of breath or cough. A key hallmark is their variability. Symptoms commonly worsen at night and in the early morning. Asthmatic symptoms usually worsen with changes in weather, laughter, fumes, smoke, smells, exercise and exposure to allergens.
Asthma is a heterogeneous disease and its symptoms and intensity vary between patients of different phenotypes/characteristics, particularly age and body mass.
Symptoms are your point of departure. Pulmonary function testing is the next crucial step to validating the diagnosis. Documentation of excessive variability in peak expiratory flows and reversibility to bronchodilators is necessary at onset of disease management. If symptoms still support asthma but have normal lung function, we should test for airway hyper responsiveness. These tests are very sensitive but poorly specific for asthma hence symptoms always remain your point of reference. A failure to demonstrate airway hyper responsiveness does support an argument against active asthma. Currently methacholine bronchoprovocation is the preferred test but mannitol is theoretically preferred if specifically looking for exercise induced bronchoconstriction.
What does Asthma control mean? Patient’s perception vs. doctor’s perception
Current recommendations have moved beyond solely recording a patient’s reported control. It’s now recommended we establish 2 key components, patient’s symptom control and estimating patient’s future risk for adverse outcomes.
Symptom control should be documented during every patient-physician contact as either well-controlled, partially controlled or uncontrolled (Slide 1). The history should be taken with direct questioning as there is definite discordance between a patient’s perception of their asthma control and the doctor’s formal understanding of well controlled asthma. Fletcher et al surveyed 1083 asthmatics recently, of which 79% described their asthma control as “good”. On further questioning, 65% had experienced ‘frequent’ day-time symptoms, 37% had ‘frequent’ nocturnal symptoms and 25% had recent exacerbations; 41% used their reliever inhaler ≧ 1/day(9). This built on a smaller Irish study Asthma Insights and Reality in Ireland which showed asthma control was equally suboptimal when challenged despite patient’s self reassurance.
Management of chronic asthma
Inhaled corticosteroids are the foundation of pharmacotherapy for asthma. Management of asthma though is not that straightforward. Its broadly focused on 3 tangents of care:
1. Accurate diagnosis and pharmacotherapy.
2. Good inhaler adherence including inhaler technique and daily compliance.
3. Ascribe a phenotype which best fits patient’s asthma to guide management going forward.
Asthma control can only be achieved by combining good patient education and long-term pharmacotherapy.
Patients must be empowered with the tools for guided self-management. The Asthma Society of Ireland (ASI) is committed to helping us educate both patients and their loved ones about their disease. They are currently working closely with the National Clinical Programme for Asthma in improving awareness and providing a range of services including free advice via their Asthma Adviceline, asthma clinics, online resources and even advocating for better resources for asthmatics.
Regular structured reviews, help improve asthma control. A significant proportion of patients do not use their inhaler correctly hence reducing the benefits of prescribed pharmacotherapy. Costello et al showed that despite high levels of adherence, many patients had errors in inhaler technique despite personal tutoring. When these were addressed, improvements in patients’ asthma control were noted. In this era of varied inhaler devices, its ever more crucial to check adherence and inhaler technique using device specific checklists. Asthma management follows a stepwise evidenced based manner. Controller or preventer options are varied but it’s important to highlight the difference to patients. Patients commonly over rely on relievers and neglect preventers.
Managing an asthma flare
It is important for patients to be confident with self-monitoring of their symptoms and peak flows. Home peak flow monitoring should be a norm and every patient should always know their best predicted peak flow. If a patient feels they are heading into a flare; they should first increase their reliever (e.g. salbutamol inhaler use). Patients are then encouraged to either double/quadruple their inhaled corticosteroid dose for 7 to 14 days.
If symptoms fail to respond within 2-3 days, and the peak expiratory flow is less than 60% predicted of the patient’s best, patient should start prednisolone therapy for 5-7 days.
Patients should be alerted to steroid side effects like sleep disturbance, mood changes, reflux and increased appetite even during short courses.
Phenotypes in asthma
Modern management of asthma requires an attempt at ascribing a phenotype or characterizing a patient’s asthma. Initial considerations when considering a phenotype should include a patient’s age of symptom onset, gender, lung function, atopy, and exacerbation history.
The next step would be using selected biomarkers to complete the phenotype. These biomarkers include skin prick testing or RAST testing towards common aeroallergens, serum total IgE, peripheral blood eosinophil count and FeNO.
Broadly speaking, clustering analysis of large asthmatic populations have led to 3 distinct phenotypes:
Severe allergic asthma
Severe eosinophilic asthma
Severe neutrophilic asthma
The severe allergic asthmatic is the classic asthmatic known to have Th2 high inflammation.
Th2 low asthma is an apparent absence of Th2 biomarkers. One example is obese asthmatics. Research has shown Th2 low “late-onset” obese asthmatics notice improved asthma control with weight loss. We now know that the adipose tissue (increased in obese people) is a potent endocrine organ which leads to multi organ systematic dysfunction.
Phenotypes should not become permanent and infrequently challenged after one cross-sectional measurement as there is a small possibility of phenotypic instability with time.
It is imperative to differentiate uncontrolled asthma from severe asthma. Uncontrolled asthma is usually due to poor adherence and modifiable risk factors. It is important that we understand barriers to good adherence to prevent inadvertent step-up of asthma therapy. Common unintentional reasons for poor adherence are forgetfulness, cost and confusion about the prescription. Intentional reasons for non-adherence are patient fear of side-effects, the cost, cultural issues with regular pharmacotherapy and finally perceived lack of need of regular controller/preventer inhalers.
Modifiable risk factors which lead to uncontrolled asthma include smoking, non-steroidal anti-inflammatories (ibuprofen, diclofenac etc.), allergens, beta-blockers and include rhinitis, obesity and uncontrolled reflux.
If a patient’s asthma remains uncontrolled, despite tackling the above and staying on the maximal ICS/LABA therapy for 3-6 months, this is considered severe asthma.
Anti-IgE monoclonal antibody or omalizumab(Xolair) is effective in severe allergic asthmatics. Xolair is like an IgE sponge. It blocks IgE, a pathogenic antibody in asthma from binding with cells like mast cells which leads to airway inflammation.
2 new antibodies directed against IL-5 has been shown to reduce severe exacerbations in severe eosinophilic asthmatics. These are subcutaneous mepolizumab and intravenous reslizumab.
Biomarkers in asthma
The way forward in asthma management is blood biomarkers and volatile organic compounds in exhaled breath e.g. FeNO. The most useful biomarker now is blood eosinophils which support both an allergic and eosinophilic phenotype.
IgE is an antibody biomarker which is increased in allergic diseases mainly asthma. Unfortunately increased levels of IgE do not correlate well with severity of asthmatic symptoms.
A biomarker which is seeing increasing use is exhaled nitric oxide (FENO). FENO is generated by the conversion of L-arginine to L-citrulline via the action of inducible nitric oxide synthase (iNOS). Nitric oxide or NO is the largest vasodilator of the pulmonary circulation. FeNo is also raised in both allergic and eosinophilic phenotypes.
Serum periostin is a matricellular protein which has increased expression in Th2 asthma or allergic asthma.
Future therapies in asthma
There are currently multiple monoclonal antibodies in clinical trial stage awaiting approval for severe asthma. Potential newcomers to the asthma armamentarium are benralizumab (IL-5 blocker), dupilumab (blocks IL-13 and IL-4), lebrikizumab and tralokinumab both targeting IL-13. All these antibody treatments are targeted at the Th2 high asthmatic.
The last international guidelines have also recommended that sublingual immunotherapy be considered in adult asthmatics with concomitant allergic rhinitis who are allergic to house dust mite and exacerbate despite maximal inhaled pharmacotherapy.