MORPHOLOGYThemorphologicchangesinasthmahavebeendescribedinindividualswhodieofprolongedsevereattacks(statusasthmaticus)andinmucosalbiopsyspecimensofindividualschallengedwithallergens.Infatalcases,thelungsaredistendedduetoairtrapping(overinflation),andtheremaybesmallareasofatelectasis.Themoststrikingfindingisocclusionofbronchiandbronchiolesbythick,tenaciousmucous plugs containingwhorlsofshedepithelium(Curschmann spirals). NumerouseosinophilsandCharcot-Leyden crystals (crystalloidsmadeupoftheeosinophilproteingalectin-10)alsoarepresent.Othercharacteristicmorphologicchangesinasthma(
Fig.13.10B ),collectivelycalledairwayremodeling,include
Fig.13.11
An attack of asthma is characterized by severe dyspnea and wheezing due to bronchoconstriction and mucus plugging, which leads to trapping of air in distal airspaces and progressive hyperinflation of the lungs. In the usual case, attacks last from 1 to several hours and subside either spontaneously or with therapy. Intervals between attacks are characteristically free from overt respiratory difficulties, but persistent, subtle deficits can be detected by pulmonary function tests. Occasionally a severe paroxysm occurs that does not respond to therapy and persists for days and even weeks (status asthmaticus). The associated hypercapnia, acidosis, and severe hypoxia may be fatal, although in most cases the condition is more disabling than lethal. Standard therapies include anti-inflammatory drugs, particularly glucocorticoids, and bronchodilators such as beta-adrenergic drugs and leukotriene inhibitors (recall that leukotrienes are potent bronchoconstrictors). Agents that block specific immune mediators, such as IL-4 and IL-5, are of modest benefit in some patients but are not broadly efficacious, perhaps because of disease heterogeneity. Another approach called bronchial thermoplasty, which involves controlled delivery of thermal energy during bronchoscopy to reduce the mass of smooth muscle and airway responsiveness, is being evaluated in patients with severe, poorly controlled asthma.
Fig. 13.11 Bronchialbiopsyspecimenfromanasthmaticpatientshowingsub–basementmembranefibrosis,eosinophilicinflammation,andsmoothmusclehyperplasia.
Asthmaischaracterizedbyreversiblebronchoconstrictioncausedbyairwayhyperresponsivenesstoavarietyofstimuli.
AtopicasthmamostofteniscausedbyaTH2andIgE-mediatedimmunologicreactiontoenvironmentalallergensandischaracterizedbyearly-phase(immediate)andlate-phasereactions.TheTH2cytokinesIL-4,IL-5,andIL-13areimportantmediators.Non-TH2inflammationalsohasrolesinatopicasthmathatarebeingdefined.
Triggersfornonatopicasthmaarelessclearbutincludeviralinfectionsandinhaledairpollutants,whichalsocantriggeratopicasthma.
Eosinophilsarekeyinflammatorycellsfoundinalmostallsubtypesofasthma;eosinophilproducts(suchasmajorbasicprotein)areresponsibleforairwaydamage.
Airwayremodeling(sub-basementmembranethickeningandhypertrophyofbronchialglandsandsmoothmuscle)addsanirreversiblecomponenttotheobstructivedisease.