Identifying an Inciting Antigen Is Associated With Improved Survival in Patients With Chronic Hypersensitivity Pneumonitis

Abstract

H ypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized pathologically by varying degrees of inflammation and/or fi brosis that result from the inhalation of an antigen to which a person has been previously sensitized. The clinical expression of HP can vary and includes acute, sub acute, and chronic forms. Symptom onset that coincides with antigen exposure provides the fi rst diagnostic clue; however, despite an exhaustive search, a recognizable, temporal relationship (between exposure and symptoms) is frequently absent, particularly in patients who present with the chronic form of HP.Chronic HP, characterized clinically by ventilatory restriction and, most commonly, upper-zonepredominant fi brosis on high-resolution CT (HRCT) scan, is irreversible and often progressive. It is believed that continued exposure to an inciting antigen (IA) perpetuates progression and the development of fi brosis in HP, but this belief hinges more on scientific rationale than systematic research. In this study, we hypothesized that among patients with histologic and Background: The cornerstone of hypersensitivity pneumonitis (HP) management is having patients avoid the inciting antigen (IA). Often, despite an exhaustive search, an IA cannot be found. The objective of this study was to examine whether identifying the IA impacts survival in patients with chronic HP. Methods: We used the Kaplan-Meier method to display, and the log-rank test to compare, survival curves of patients with well-characterized chronic HP stratifi ed on identifi cation of an IA exposure. A Cox proportional hazards (PH) model was used to identify independent predictors in time-todeath analysis. Results: Of 142 patients, 67 (47%) had an identifi ed IA, and 75 (53%) had an unidentifi ed IA. Compared with survivors, patients who died (n 5 80, 56%) were older, more likely to have smoked, had lower total lung capacity % predicted and FVC % predicted, had higher severity of dyspnea, were more likely to have pulmonary fi brosis, and were less likely to have an identifi able IA. In a Cox PH model, the inability to identify an IA (hazard ratio [HR], 1.76; 95% CI, 1.01-3.07), older age (HR, 1.04; 95% CI, 1.01-1.07), the presences of pulmonary fi brosis (HR, 2.43; 95% CI, 1.36-4.35), a lower FVC% (HR, 1.36; 95% CI, 1.10-1.68), and a history of smoking (HR, 2.01; 95% C1, 1.15-3.50) were independent predictors of shorter survival. After adjusting for mean age, presence of fi brosis, mean FVC%, mean diffusing capacity of the lung for carbon monoxide (%), and history of smoking, survival was longer for patients with an identifi ed IA exposure than those with an unidentifi ed IA exposure (median, 8.75 years vs 4.88 years; P 5 .047). Conclusions: Among patients with chronic HP, when adjusting for a number of potentially infl uential predictors, including the presence of fi brosis, the inability to identify an IA was independently associated with shortened survival. CHEST 2013; 144(5):1644-1651Abbreviations: D lco 5 diffusing capacity of the lung f...

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

“…Furthermore, in 25-60% of HP cases no cause is ever identified [191]. Additionally, not everyone chronically exposed to inhaled particulate develops HP, which suggests an underlying predisposition.…”

“…Average survival with HP is highly dynamic and depends significantly on whether the trigger is identified. The average survival in individuals with HP and a known trigger is 18 years while those with unknown triggers have a survival of only 9 years [191]. Morphological characterization of chronic HP indicates that it closely resembles IPF in that it can contain UIP and fibrotic patches and has a poorer outcome than acute HP [194].…”

Hypersensitivity pneumonitis: Diagnostic criteria, treatment, prognosis and prevention

“…Niezidentyfikowanie antygenu przyczynia się do wzrostu śmiertelności. U chorych z postacią przewlekłą AZPP i niezidentyfikowanym antygenem przeżycie wynosi średnio 4,88 lat (u chorych z wykrytym antygenem -do 8,75 roku) [40]. Nadciśnienie płucne występuje u ok. 20% chorych z przewlekłą postacią AZPP i zwiększa u nich ryzyko zgonu [41].…”

Toll-like Receptors 2 and 9 Are Important for Innate Immune Cell Activation and Recruitment in Hypersensitivity Pneumonitis

“…If exposure can be stopped, patients with acute and subacute HP will recover. In chronic HP, antigen identification and avoidance will not completely resolve symptoms but is associated with reduced mortality (Fernandez Perez et al, 2013). Corticosteroids are also often prescribed, but have little effect on disease outcomes (Kokkarinen et al, 1992).…”

“…CHP is progressive and irreversible and is associated with high morbidity and mortality (Hanak et al, 2008;Vourlekis et al, 2004). At this stage, antigen avoidance will not resolve symptoms but can prolong survival (Fernandez Perez et al, 2013). Deaths where HP is the underlying or contributing cause have steadily increased from 1979 to 2007(NIOSH., 2012.…”