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The first few cases of hypersensitivity pneumonitis (HP) were described in the early 20th century in farmers exposed to moldy hay or straw. As then, HP has been ascribed to multiple inhaled antigens found in a large variety of environmental settings. Hypersensitivity pneumonitis results from an exaggerated immune response, which gives rise to acute infection‐like symptoms or to progressive, sometimes irreversible lung damage. The diagnosis is based on a combination of clinical characteristics of the disease. Clinical diagnostic criteria have recently been published. The immune mechanisms leading to HP are still incompletely understood. Initially, believed to be a classes III and IV immune response, we now have a clearer understanding of the complex inflammatory events involved. These include the release of pro inflammatory cytokines and a decrease in the immune control mechanisms via surfactant, dendritic and T‐regulatory cells. Despite the improved understanding, the treatment and outcome of HP have not changed. Oral corticosteroids remain the only effective drugs and contact withdrawal constitutes the ideal solution. If unchecked, HP can lead to irreversible lung damage in the form of fibrosis or emphysema, respiratory insufficiency and even death.

We have documented changes in expression of collagenolytic/gelatinolytic enzymes of the matrix metalloproteinase family (MMP) in healing or ulcerating corneal wounds of rat or rabbit. Correlation of our findings with specific changes in the extracellular matrix of the repair tissue suggests two different roles for the enzymes, MMP-2 and MMP-9. MMP-2 is expressed in undamaged corneal stroma where it may degrade the occasional collagen molecule that becomes damaged. After corneal wounding, expression of this enzyme is increased and much of it appears in the active form. These changes persist for at least seven months, suggesting that MMP-2 is involved in the prolonged process of collagen remodelling in the stromal repair tissue. MMP-9 is expressed in the epithelial layer of repair tissue with a timing suggesting it might participate in controlling resynthesis of the basement membrane. MMP-9 also appears to be involved in degradation of the epithelial basement membrane that precedes corneal ulceration.

Hypersensitivity pneumonitis (HP) is characterised by lung lymphocytosis. Most individuals exposed to HP antigens remain asymptomatic. The mechanisms involved in the impaired immune tolerance leading to HP are unclear. Normally, T-regulatory (Treg)-cells control the immune response. The aim of the present study was to determine whether Treg-cell suppressive function deficiency can explain the uncontrolled inflammation in HP.Bronchoalveolar lavage (BAL) and blood samples were obtained from normal subjects, asymptomatic individuals and HP patients. BAL and blood Treg-cells were isolated. The ability of Treg-cells to suppress T-cell proliferation and the role of interleukin (IL)-17 was verified.BAL and blood Treg-cells from normal subjects suppressed the proliferative response of activated T-cells by 47.1 and 42%, respectively. BAL and blood Treg-cells from asymptomatic subjects had a slightly decreased activity and suppressed proliferation by 29.4 and 31.8%, respectively. BAL and blood Treg-cells from HP patients were totally nonfunctional and unable to suppress proliferation. Low levels of IL-17 were detected in sera and BAL from both normal and asymptomatic individuals, whereas measurable levels were found in patients.Treg-cells may be involved in antigen tolerance in asymptomatic subjects. Defective Treg-cell function, potentially caused by increased IL-17 production, could account for the exacerbated immune response characteristic of HP.

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The review will help clinicians in their diagnostic approach to hypersensitivity pneumonitis and lead them to look for other potential sources of the disease. The findings described will help guide further research on the pathophysiology and seek new treatments for this worldwide orphan disease.

Most of the mechanisms involved in the pathogenesis of hypersensitivity pneumonitis remain incompletely understood. Current and future findings will not only help our understanding of the disease and its prevention, but also improve its treatment.

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