pulmonary disorders
Asthma
Pathophysiology of Asthma
Asthma involves Bronchoconstriction Airway edema and inflammation Airway hyperreactivity Airway remodeling In patients with asthma, TH2 cells and other cell types—notably, eosinophils and mast cells, but also other CD4+ subtypes and neutrophils—form an extensive inflammatory infiltrate in the airway epithelium and smooth muscle, leading to airway remodeling (ie, desquamation, subepithelial fibrosis, angiogenesis, smooth muscle hypertrophy). Hypertrophy of smooth muscle narrows the airways and increases reactivity to allergens, infections, irritants, parasympathetic stimulation (which causes release of proinflammatory neuropeptides, such as substance P, neurokinin A, andcalcitoningene-related peptide), and other triggers of bronchoconstriction. Additional contributors to airway hyperreactivity include loss of inhibitors of bronchoconstriction (epithelium-derived relaxing factor, prostaglandin E2) and loss of other substances called endopeptidases that metabolize endogenous bronchoconstrictors. Mucus plugging and peripheral blood eosinophilia are additional classic findings in asthma and may be epiphenomena of airway inflammation. However, not all patients with asthma have eosinophilia. Common triggers of an asthma exacerbation include Environmental and occupational allergens (numerous) Cold, dry air Infections Exercise Inhaled irritants Emotion Aspirinand other nonsteroidal anti-inflammatory drugs (NSAIDs) Gastroesophageal Reflux Disease (GERD) (GERD) Infectious triggers in young children include Respiratory Syncytial Virus (RSV) and Human Metapneumovirus Infections , rhinovirus, and parainfluenza virus infection. In older children and adults, upper respiratory infections (particularly with rhinovirus) and pneumonia are common infectious triggers. Exercise can be a trigger, especially in cold or dry environments, and cold air alone can also trigger symptoms. Inhaled irritants, such as air pollution, cigarette smoke, perfumes, and cleaning products can also trigger symptoms in patients with asthma. (Inhaled irritants that trigger asthma exacerbations do so by inducing a T2 response, in contrast to what happens in reactive airways dysfunction syndrome and chronic irritant-induced asthma.) Emotions such as anxiety, anger, and excitement sometimes trigger exacerbations. Aspirinis a trigger in up to 30% of patients with severe asthma and in < 10% of all patients with asthma.Aspirin-sensitive asthma is typically accompanied by nasal polyps with nasal and sinus congestion, which is a condition also known as Samter's triad (asthma, nasal polyps, and sensitivity toaspirinand NSAIDs). GERD is a common trigger among some patients with asthma, possibly via esophageal acid-induced reflex bronchoconstriction or by microaspiration of acid. However, treatment of asymptomatic GERD (eg, with proton pump inhibitors) does not seem to improve asthma control. Allergic rhinitis often coexists with asthma; it is unclear whether the two are different manifestations of the same allergic process or whether rhinitis is a discrete asthma trigger. In the presence of triggers, there is reversible airway narrowing and uneven lung ventilation. In lung regions distal to narrowed airways, relative perfusion exceeds relative ventilation; thus, alveolar oxygen tensions fall and alveolar carbon dioxide tensions rise. Usually, such regional hypoxia and hypercarbia trigger compensatory pulmonary vasoconstriction to match regional ventilation and perfusion; however, these compensatory mechanisms fail during an asthma exacerbation due to the vasodilatory effects of prostaglandins that are upregulated during an exacerbation. Most patients can compensate by hyperventilating, but in severe exacerbations, diffuse bronchoconstriction causes severe gas trapping, and the respiratory muscles are put at a marked mechanical disadvantage so that the work of breathing increases. Under these conditions, hypoxemia worsens and PaCO2 rises. Respiratory Acidosis and 