Hypersensitivity pneumonitis: Current concepts in pathogenesis, diagnosis, and treatment

Abstract

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) caused by an inhalational exposure to low-molecular weight compounds, which occurs in susceptible individuals. Hypersensitivity pneumonitis may present in two forms: acute, predominantly inflammatory HP (non-fibrotic HP), and chronic or fibrotic HP (fibrotic HP). 1 Some patients will experience a self-limiting acute HP course, whereas others, given sufficient time and exposure, will progress from non-fibrotic to fibrotic disease, and still other patients may present with established fibrotic HP without a clear acute episode of exposure. This suggests that the pathophysiology of HP is contributed by complex pathways of antigen exposure, aberrant immunological mechanisms, and genetic predispositions. | EpidemiologyReported estimates of the incidence of HP vary across populations, with 1-3 per 100,000 people per year (including children) in Denmark, 2 11.5 per 100,000 people over 65 years per year in the USA, 3 and up to 30 per 100,000 people per year in New Mexico. 4 HP is the third most common ILD after idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). 5 The estimated prevalence of HP is higher in at-risk

The Impact of Ambient Environmental and Occupational Pollution on Respiratory Diseases

“…Certain organic chemicals and low molecular weight compounds can cause HP [ 93 ]. The incidence of HP ranges from to 1–3 to 30 per 100,000 people per annum [ 94 , 95 , 96 ].…”

“…During the transition from acute, predominantly inflammatory HP to chronic or fibrous HP, fibroblast proliferation is promoted by chemotactic factors produced by granulomas, switching from a Th1 to Th2 inflammatory response, a decrease in regulatory T cells, production of cytotoxic CD8 + T cells, and differentiation of Th17 cells. Fibroblasts then differentiate into myofibroblasts, producing collagen and extracellular matrix components, which promotes pulmonary fibrosis [ 93 ]. In addition, gene variants, including the tumor necrosis factor (TNF)-gene promotor region [ 107 ], overexpression of mucin 5 subtype B (MUC5B) [ 108 ], and telomere dysfunctions [ 109 ], are involved as genetic risk factors in individuals susceptible to fibrotic HP.…”

Diagnosing interstitial lung disease by multidisciplinary discussion: A review

“… a See References ( 1 , 3 – 8 , 39 ) . b Including antibodies to extractable nuclear antigens (anti-Ro [SS-A], anti-La [SS-B], anti-Smith, antiribonucleoprotein [anti-RNP], antitopoisomerase [Scl-70], anti-Jo-1), anti-double stranded DNA antibodies (anti-dsDNA), anti-tRNA synthetase antibodies (Jo-1, PL-7, PL-12, EJ, OJ, KS, Zo, tRS), extended myositis panel (including antibodies to Ro-52, Ku, Mi-2, TIF1- γ , PM-Scl, MDA-5, NXP2, SAE1) and anti-neutrophil cytoplasmic antibody (ANCA) ( 7 , 40 ) .…”

Environmental and occupational exposures in interstitial lung disease

“…The mechanisms of disease in hypersensitivity pneumonitis, while not fully elucidated, are believed to arise as a result of inhaled antigens triggering granuloma formation, an exuberant inflammatory response and/or fibroblast proliferation and pulmonary fibrosis. The most common recognized antigenic causes of hypersensitivity pneumonitis are birds, mould, farming and contaminated metal working fluids [12]. Cases of nonfibrotic hypersensitivity pneumonitis frequently have a clear temporal association between exposure and symptom onset, with established resolution after antigen remediation or removal.…”