Etiology
Multiple causative agents have been identified. The two most commonly reported agents are bacteria (e.g., thermophilic Actinomycetes, responsible for a variety of syndromes including farmer's lung, bagassosis, and mushroom picker's lung) and animal proteins (e.g., avian proteins responsible for diseases including pigeon breeder's lung, bird fancier's lung, and budgerigar fancier's disease), with exposure to large farm animals also implicated.[13]
Fungi have also been reported as antigenic sources, and reactive chemicals such as acid anhydrides (epoxy resin lung disease), diisocyanates, and agents used in metalworking are also known causes of HP syndromes.[14][15][16][17] In the UK, exposure to metalworking fluid has become the most common cause of occupational HP, accounting for about one-half of all cases.[18] Ingested drugs such as nitrofurantoin, methotrexate, roxithromycin, and rituximab can cause drug-induced HP syndrome.[19] Furthermore, a published case report has described herbal supplementation with ayurvedic medicine as a cause of HP.[20] A 2018 case of sertraline-induced HP was reported.[21]
Case reports indicate a possible association between the use of electronic nicotine delivery systems (vaping) and HP.[22] One case report describes the clinical presentation of HP associated with sertraline.[23] HP has been reported in a person who consumed ayurvedic medicine.[20]
Pathophysiology
The immunopathogenic mechanisms that result in the characteristic inflammation of HP are not fully understood. The relative contributions of humoral and cellular response are unclear. The likely important role of cellular adaptive immunity as the cause of HP is supported by the fact that individuals with hypogammaglobulinemia can develop HP. Bronchoalveolar lavage studies in symptomatic HP patients suggest that important cells involved are CD3+ T lymphocytes that are either CD8+ or CD4+ with a Th1 phenotype.[24][25][26][27]
The inflammation of HP has a characteristic, but not pathognomonic, appearance. The cellular infiltrate consists primarily of lymphocytes, plasma cells, and neutrophils. In addition, there are noncaseating granulomas and activated foamy macrophages. The inflammation tends to be bronchocentric or bronchiolocentric in distribution. In later stages, the lymphocytic alveolitis is less prominent, and commonly there is interstitial fibrosis with collagen-thickened bronchiolar walls.
Early in the disease, the fever, tachypnea, dyspnea, pulmonary infiltrates, restrictive pulmonary function tests (PFTs), and reduced diffusing lung capacity of carbon monoxide (DLCO) are all due to the lymphocytic alveolitis.
Over time, the inflammation becomes less intense, with the insidious development of malaise, weight loss, dyspnea, cough, a mixed PFT picture, and decreased DLCO.[28][29][30]
Classification
Types of hypersensitivity pneumonitis (HP)[3]
Consensus among experts regarding disease definition and diagnostic criteria is lacking, but the American Thoracic Society, Japanese Respiratory Society, and Latin American Thoracic Association diagnostic guidelines published in 2020 classify patients as having fibrotic or nonfibrotic HP:
Nonfibrotic (purely inflammatory; the absence of radiologic and/or histopathologic evidence of fibrosis)
Fibrotic (the presence of radiologic and/or histopathologic evidence of fibrosis).
Where patients have mixed features, categorization is determined by the predominance of these features.
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