PART D. MANAGING ASTHMA WITH COMORBIDITIES AND IN SPECIFIC POPULATIONS KEY POINTS
MANAGING COMORBIDITIES
Several comorbidities are commonly present in patients with asthma, particularly those with difficult-to-treat or severe asthma.87 Active management of comorbidities is recommended because they may contribute to symptom burden, impair quality of life, and lead to medication interactions. Some comorbidities also contribute to poor asthma control.384 Obesity
Clinical features
Asthma is more difficult to control in obese patients.315-318 This may be due to a different type of airway inflammation, contributory comorbidities such as obstructive sleep apnea and gastroesophageal reflux disease (GERD), mechanical factors, or other as yet undefined factors. In addition, lack of fitness and reduction in lung volume due to abdominal fat may contribute to dyspnea.
Diagnosis
Document body mass index (BMI) for all patients with asthma. Because of other potential contributors to dyspnea and wheeze in obese patients, it is important to confirm the diagnosis of asthma with objective measurement of variable airflow limitation (Box 1-2, p.19). Asthma is more common in obese than non-obese patients,48 but both over- and under-diagnosis of asthma occur in obesity.29,49
Management
As for other patients with asthma, ICS are the mainstay of treatment in obese patients (Evidence B), although their response may be reduced.318 Weight reduction should be included in the treatment plan for obese patients with asthma (Evidence B). Increased exercise alone appears to be insufficient (Evidence B);323 however a weight loss program plus twice-weekly aerobic and strength exercises improved symptom control, lung function and inflammatory markers compared with weight loss alone (Evidence B).324 Weight loss improves asthma control, lung function, health status and reduces medication needs in obese patients,319,320 but the quality of some studies is poor. The most striking results have been observed after bariatric surgery,321,322 but even 5–10% weight loss can lead to improved asthma control and quality of life.323
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Gastroesophageal reflux disease (GERD) Clinical features
GERD can cause symptoms such as heartburn, and epigastric or chest pain, and is also a common cause of dry cough.
Symptoms and/or diagnosis of GERD are more common in people with asthma than in the general population,384 but this may be in part due to cough being attributed to asthma; in addition, some asthma medications such as beta2 -agonists and theophylline cause relaxation of the lower esophageal sphincter. Asymptomatic gastroesophageal reflux is not a likely cause of poorly controlled asthma.384
Diagnosis
In patients with confirmed asthma, GERD should be considered as a possible cause of a dry cough; however, there is no value in screening patients with uncontrolled asthma for GERD (Evidence A). For patients with asthma and
symptoms suggestive of reflux, an empirical trial of anti-reflux medication, such as a proton pump inhibitor or motility agent, may be considered, as in the general population. If the symptoms do not resolve, specific investigations such as 24-hour pH monitoring or endoscopy may be considered.
Management
A review of proton pump inhibitors in patients with confirmed asthma, most of whom had a diagnosis of GERD, showed a significant but small benefit for morning PEF, but no significant benefit for other asthma outcomes.385 In a study of adult patients with symptomatic asthma but without symptoms of GERD, treatment with high-dose proton pump
inhibitors did not reduce asthma symptoms or exacerbations.386 In general, benefits of proton pump inhibitors in asthma appear to be limited to patients with both symptomatic reflux and night-time respiratory symptoms.387 Other treatment options include motility agents, lifestyle changes and fundoplication. In summary, symptomatic reflux should be treated, but patients with poorly controlled asthma should not be treated with anti-reflux therapy unless they also have
symptomatic reflux (Evidence A). Few data are available for children with asthma symptoms and symptoms of GERD.388,389
Anxiety and depression Clinical features
Psychiatric disorders, particularly depressive and anxiety disorders, are more prevalent among people with asthma.390 Psychiatric comorbidity is also associated with worse asthma symptom control and medication adherence, and worse asthma-related quality of life.391 Anxious and depressive symptoms have been associated with increased asthma-related exacerbations and emergency visits.392 Panic attacks may be mistaken for asthma.
Diagnosis
Although several tools are available for screening for anxious and depressive symptomatology in primary care, the majority have not been validated in asthma populations. Difficulties in distinguishing anxiety or depression from asthma symptoms may therefore lead to misdiagnosis. It is important to be alert to possible depression and/or anxiety in people with asthma, particularly when there is a previous history of these conditions. Where appropriate, patients should be referred to psychiatrists or evaluated with a disease-specific psychiatric diagnostic tool to identify potential cases of depression and/or anxiety.
Management
There have been few good quality pharmacological and non-pharmacological treatment trials for anxiety or depression in patients with asthma, and results are inconsistent. A Cochrane review of 15 randomized controlled trials of
psychological interventions for adults with asthma included cognitive behavior therapy, psychoeducation, relaxation, and biofeedback.393 Results for anxiety were conflicting, and none of the studies found significant treatment differences for depression. Drug treatments and cognitive behavior therapy394 have been described as having some potential in patients with asthma; however, current evidence is limited, with a small number of studies and methodological shortcomings.
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Food allergy and anaphylaxis Clinical features
Rarely, food allergy is a trigger for asthma symptoms (<2% of people with asthma). In patients with confirmed food-induced allergic reactions (anaphylaxis), co-existing asthma is a strong risk factor for more severe and even fatal reactions. Food-induced anaphylaxis often presents as life-threatening asthma.89 An analysis of 63 anaphylaxis-related deaths in the United States noted that almost all had a past history of asthma; peanuts and tree nuts were the foods most commonly responsible.395 A UK study of 48 anaphylaxis-related deaths found that most were regularly treated for asthma, and that in most of these, asthma was poorly controlled.396
Diagnosis
In patients with confirmed food allergy, it is important to assess for asthma. Children with food allergy have a four-fold increased likelihood of having asthma compared with children without food allergy.397 Refer patients with suspected food allergy or intolerance for specialist allergy assessment. This may include appropriate allergy testing such as skin prick testing and/or blood testing for specific IgE. On occasion, carefully supervised food challenges may be needed.
Management
Patients who have a confirmed food allergy that puts them at risk for anaphylaxis must be trained and have an
epinephrine auto-injector available at all times. They, and their family, must be educated in appropriate food avoidance strategies, and in the medical notes, they should be flagged as being at high risk. It is especially important to ensure that their asthma is well controlled, they have a written action plan, understand the difference between asthma and
anaphylaxis, and are reviewed on a regular basis.
Rhinitis, sinusitis and nasal polyps Clinical features
Evidence clearly supports a link between diseases of the upper and lower airways.398 Most patients with asthma, either allergic or non-allergic, have concurrent rhinitis, and 10–40% of patients with allergic rhinitis have asthma.399 Depending on sensitization and exposure, allergic rhinitis may be seasonal (e.g. ragweed or grass pollen), perennial (e.g. mite allergens), or intermittent (e.g. furred pets).398
Rhinitis is defined as irritation and inflammation of the mucous membranes of the nose. Allergic rhinitis may be accompanied by ocular symptoms (conjunctivitis). Rhinosinusitis is defined as inflammation of the nose and paranasal sinuses characterized by more than two symptoms including nasal blockage/obstruction and/or nasal discharge (anterior/posterior nasal drip).400 Other symptoms may include facial pain/pressure and/or a reduction or loss of smell.
Sinusitis rarely occurs in the absence of rhinitis.
Rhinosinusitis is defined as acute when symptoms last <12 weeks with complete resolution, and chronic when symptoms occur on most days for at least 12 weeks without complete resolution. Chronic rhinosinusitis is an
inflammatory condition of the paranasal sinuses that encompasses two clinically distinct entities: chronic rhinosinusitis without nasal polyposis and chronic rhinosinusitis with nasal polyposis.401 The heterogeneity of chronic rhinosinusitis may explain the wide variation in prevalence rates in the general population ranging from 1–10% without polyps and 4%
with polyps. Chronic rhinosinusitis is associated with more severe asthma, especially in patients with nasal polyps.402 Diagnosis
Rhinitis can be classified as either allergic or non-allergic depending on whether allergic sensitization is demonstrated.
Variation in symptoms by season or with environmental exposure (e.g. furred pets) suggests allergic rhinitis.
Examination of the upper airway should be arranged for patients with severe asthma.
Management
Evidence-based guidelines (Allergic Rhinitis in Asthma, ARIA)403 recommend intranasal corticosteroids for treatment of allergic rhinitis. In a case-control study, treatment of rhinitis with intranasal corticosteroids was associated with less need
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for asthma-related hospitalization and emergency department visits,404 but a meta-analysis found improvement in asthma outcomes only in patients not also receiving ICS.405 However, few placebo-controlled studies have
systematically evaluated the effect of proper treatment and management of chronic rhinosinusitis on asthma control. A recent placebo-controlled trial of nasal mometasone in adults and children with chronic rhinosinusitis and poorly-controlled asthma showed no benefit for asthma outcomes, suggesting that, while chronic rhinosinusitis can contribute to respiratory symptoms, e.g. chronic cough, its treatment in patients with asthma should be targeted at the symptoms of rhinosinusitis rather than to improve asthma control.406