Asthma and Chronic Obstructive Pulmonary Disease

Introduction

Asthma is a common chronic lung disease that affects individuals of all ages. Previously, asthma was considered a disease primarily of children and young adults. Recent epidemiologic studies have dispelled this notion. The increased prevalence of asthma in older adults is the result of increased survival of children and young adults with asthma, a higher number of people with adult-onset asthma, and increased awareness among clinicians. Despite the recent attention placed on asthma as a lung disease that can affects older adults, underdiagnosis and misdiagnosis are still common. Clinically, asthma at older ages is associated with greater morbidity, greater mortality, and higher health care costs than in younger individuals. The presence of multiple morbidities and frailty contribute to diagnostic confusion and complicates management. More research is needed to help clinicians confront this growing challenge.

Asthma was defined by consensus in the 2014 GINA report as “a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, chest tightness, shortness of breath, and cough that vary of time and intensity, together with variable expiratory airflow limitation.” Many different asthma phenotypes exist, including allergic asthma, non-allergic asthma, late or adult-onset asthma, occupational asthma, and asthma with fixed airway obstruction (often misdiagnosed as COPD). Although allergic asthma, in particular, more commonly has its onset in childhood, any of the asthma phenotypes can be seen in older people.

Epidemiology

Globally, asthma is conservatively estimated to affect 300 million people of all ages and ethnicities with wide variability in prevalence from country to country, ranging from 1% to 18% of the population. The prevalence of asthma has been rising for several decades, in parallel with increases in rates of allergy and changes (modernization and urbanization) in living conditions of the world's population. In the United States, population survey estimates of the prevalence of physician-diagnosed asthma in older adults have ranged from 4% to 11%, disproportionally affecting women. Most surveys have relied on subjects reporting a physician diagnosis of asthma, which has its limitations, particularly in older adults. Asthma may be underdiagnosed because of misclassification as other conditions (e.g., COPD, heart disease), underreporting of symptoms by older individuals, and underuse of objective tests (e.g., spirometry) to confirm a clinical diagnosis. Asthma can also be overdiagnosed; a randomly sampled population study of physician-diagnosed asthma in Canada found no objective evidence of current asthma in one third of subjects studied. Older age at time of asthma diagnosis was associated with an overdiagnosis of asthma. Despite these limitations of epidemiologic studies, it is apparent that asthma affects a significant percentage of older individuals and that the numbers are expected to continue to rise over the coming years.

Asthma in older people places a high burden on both patients and society. Older adults with asthma have higher rates of hospitalization and proportionally increased health care costs compared to younger adults and children with asthma. In part, this relates to the complexity of management of asthma in the setting of multiple comorbidities. According to the U.S. Centers for Disease Control and Prevention, asthma deaths in older adults account for more than 50% of asthma fatalities annually, with an approximately 5.8 asthma deaths per 100,000 reported in the years 2001 through 2003. Mortality rates have been estimated to be fourfold higher in individuals older than 65 years compared to adults with asthma who are younger than 65 years, with a tendency for higher mortality rates in women.

Pathophysiology

Asthma is a heterogeneous condition that develops from complex interactions among genotypic and environmental factors. A number of candidate genes have been identified that predispose to asthma. Environmental risk factors that play a role in asthma pathogenesis include the amount and timing of exposure to indoor and outdoor allergens, tobacco smoke, respiratory tract infections, air pollution, occupational sensitizers and irritants, and diet.

Asthma is a chronic inflammatory airway disease involving many inflammatory cells and mediators. Although the clinical expression of asthma can be variable and episodic, airway inflammation is typically a constant feature of the disease. The key inflammatory cells in asthma include mast cells, eosinophils, T lymphocytes, and macrophages. Neutrophils play a role in certain asthma phenotypes (e.g., smokers, severe and late-onset asthma). Numerous cellular mediators are released by inflammatory and structural cells in asthma, including cytokines (e.g., interleukin [IL]-4, IL-5, IL-13), cysteinyl leukotrienes, chemokines, histamine, and nitric oxide, which amplifies the inflammatory response through recruitment and activation of additional inflammatory cells. Structural airway changes are characteristic of asthma. Airway narrowing results from increased airway smooth muscle contraction, thickening of airway wall (e.g., smooth muscle hypertrophy, basement membrane thickening, edema, and inflammatory cell infiltration), and mucus hypersecretion. Another important feature of asthma is airway hyperresponsiveness, an exaggerated bronchoconstriction response to various stimuli.

The adaptive changes of the immune system with aging have implications for the pathophysiology of asthma. Traditionally, atopy (immunoglobulin E [IgE] sensitization to at least one antigen) or allergy was thought to be associated more strongly with asthma in childhood than with late-onset asthma. Total IgE levels and antigen-specific sensitization fall with normal aging. The Epidemiology and Natural History of Asthma study examined asthma in older (>65 years old) compared to younger individuals; older individuals with asthma had lower total IgE levels, fewer positive skin prick tests, and less atopic clinical conditions (e.g., allergic rhinosinusitis or atopic dermatitis). However, some recent studies have shown that older individuals with asthma are more likely to demonstrate allergen sensitization than older individuals without asthma, albeit to a lesser extent than younger individuals with asthma. The most common aeroallergens (e.g., cat, dust mite, cockroach) to which older individuals with asthma are sensitized, not surprisingly, varies based on characteristics (e.g., urban vs. rural) of the population studied. The role and importance of atopy in asthma pathogenesis in older adults clearly needs further investigation. There is also a reduction in T lymphocyte number and activity with aging; the resultant immunosenescence diminishes the effectiveness of vaccinations and increases susceptibility to viral and bacterial infection. Respiratory tract infection is an important cause of poor asthma control and exacerbations in older adults. Whether respiratory tract infections, particularly viral, are important in asthma pathogenesis in older adults, as has been proposed in children, needs further study.

Diagnosis

The diagnosis of asthma is based on clinical assessment (i.e., history and physical examination) and objective testing. Asthma symptoms tend to vary over time (often worse at night or early morning) and in intensity. Typical symptoms include wheeze, dyspnea, chest tightness, cough, and, to a lesser extent, sputum production that occur spontaneously or may be triggered by various stimuli (e.g., air quality, aeroallergens, respiratory tract infections, exercise, scents). During physical examination of people with asthma, they may exhibit normal breathing or they may show signs of airflow obstruction (e.g., wheeze, prolonged expiratory phase), hyperinflation (e.g., shortened tracheal length, barrel chest, diminished breath sound intensity), or, during severe exacerbations, increased respiratory difficulty (e.g., tachypnea, tachycardia, pulsus paradoxus, cyanosis, diaphoresis, accessory muscle use, changes in mental status). The physical examination is often more relevant to assess for conditions that may mimic asthma symptoms.

Asthma symptoms may be poorly perceived, underreported, or misinterpreted to relate to other causes in older adults. History should include assessment of risk factors for asthma, such as presence of personal or family history of atopy and occupational history. The differential diagnosis for asthma in older people is broad, as many other conditions manifest with typical symptoms of asthma ( Box 48-1 ). Differentiating asthma from COPD can be difficult at times (see Table 48-1 ). Overcoming the diagnostic challenge of asthma in older adults requires careful clinical assessment and additional objective tests beyond pulmonary function tests (PFTs) not typically required in children or young adults.

Objective testing is required to confirm a clinical suspicion of asthma. PFTs are used to demonstrate variable airflow obstruction and/or bronchial hyperresponsiveness, hallmark features of asthma. Unfortunately, PFTs may be difficult to perform in some older individuals because of physical or cognitive impairments or they may be difficult to interpret because of poor reliability of predicted normal values in this age group. Newer techniques to reliably measure pulmonary function (e.g., forced oscillometry) are being developed and validated that require less cooperation and effort on the part of the patient.