Hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an antigen to which the subject has been previously sensitized. The incidence of HP is unknown. A population-based study estimated the annual incidence of interstitial lung diseases as 30:100,000 and HP accounted for less than 2% of these cases. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence respectively, using simple diagnostic criteria. Chest X-rays may be normal in active HP; High Resolution Computed Tomography is sensitive but not specific for the diagnosis of HP. The primary use of pulmonary function tests is to determine the physiologic abnormalities and the associated impairment. Despite the pitfalls of false positive and false negatives, antigen-specific IgG antibodies analysis can be useful as supportive evidence for HP. Bronchoalveolar lavage plays an important role in the investigation of patients suspected of having HP. A normal number of lymphocytes rules out all but residual disease. Surgical lung biopsy should be reserved for rare cases with puzzling clinical presentation or for verification the clinical diagnosis when the clinical course or response to therapy is unusual. Being an immune reaction in the lung, the most obvious treatment of HP is avoidance of contact with the offending antigen. Systemic corticosteroids represent the only reliable pharmacologic treatment of HP but do not alter the long-term outcome. The use of inhaled steroids is anecdotal. Treatment of chronic or residual disease is supportive

Airborne microflora in Quebec dairy farms : lack of effect of bacterial hay preservatives

Pediococcus pentosaceus is a lactic-acid producing bacterium inoculated in hay to prevent hay deterioration. This study sought to verify the effect of this treatment on the barn microenvironment. Air samples were obtained from 19 barns using bacterial hay treatment and from 18 control barns with six-stage Andersen samplers and all-glass impingers. Appropriate culture media were used for the recovery and identification of microorganisms. Endotoxins were measured with chromogenic Limulus amoebocyte lysate assay. Median values (respectively for treated and untreated hay barns) were: 5.28 × 105 and 3.84 × 105 colony-forming units (CFU)/m3 for total bacteria; 3.18 × 106 and 4.5 × 106 CFU/m3 for molds; 1.36 × 103 and 1.74 × 103 endotoxin units/m3 for endotoxin levels; and 1.03 × 103 and 3.00 × 103 CFU/m3 for Saccharopolyspora rectivirgula. No viable P. pentosaceus were recovered. The presence of S. rectivirgula, the causative agent for farmer's lung, was not influenced by the hay treatment. Since no significant difference was observed in any of the airborne contaminants, this type of hay treatment probably does not protect farmers from the respiratory effect of ambient microbial contaminants

Seasonal variations in work-related health effects in swine farm workers

The aim of the project was to investigate whether there were diminished health effects in swine farm workers during summer compared with winter, as seasonal differences in concentrations of bioaerosols have been reported. Twenty-four workers were visited once during each season. Before and after a work shift, they underwent lung function testing and blood sampling. During work, they wore personal air sampling equipment. The mean endotoxin exposure of the workers was highest during winter (25,690 vs. 6,553 EU/m3; p = 0.004). Although exposures to endotoxin and CO2 varied between the seasons, no differences in lung function were found between them. White blood cell concentration increased over the work shift from 5.74–6.82 in winter (p < 0.0001) and from 5.80–6.38 in summer (p = 0.014). These increases differed between the two seasons (p = 0.032). Plasma tumour necrosis factor concentrations fell over the work shift only during winter (1.34–1.24 pg/ml (p = 0.03) (p = 0.014 for the difference between seasons). Plasma interleukin-6 increased over the work shift independently of season (p = 0.0006). The study supported our hypothesis of adverse effects on lung function and immune system, but less so during summer than during winter among Québec swine farm workers

Work-related health effects in swine building workers after respiratory protection use

Objective: To compare inflammation and lung function in swine workers after periods with and without respiratory protection during work. Methods: Twenty-three workers were examined before and after two nonprotected work shifts. One shift was preceded by a period with diminished exposure by use of respirators. The other shift was preceded by an unprotected period of work. Results: Endotoxin concentrations were similarly high (24,636 and 28,775 endotoxin units/m3). A 3.1% cross-shift decline in forced vital capacity occurred after the period with respiratory protection (P = 0.01). Blood leukocytes increased more (P = 0.01) and bactericidal/permeability-increasing protein was reduced (P = 0.015) only after the period with respiratory protection. Plasma interleukin-6 increased (P < 0.0001) during both visits. Conclusion: Respiratory protection resulted in cross-shift inflammatory and respiratory reactions at return to unprotected work

Effects of Asm-024, A Modulator of Acetylcholine Receptor Function, On Airway Responsiveness and Allergen-Induced Responses in Patients with Mild Asthma

OBJECTIVES: To evaluate the safety, tolerability and clinical activity of ASM-024, a new cholinergic compound with dual nicotinic and muscarinic activity, in mild allergic asthma

Le FORUM, Vol. 34 No. 4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1028/thumbnail.jp

Le Forum, Vol. 45 #4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1109/thumbnail.jp

Muramyl Dipeptide Induces NOD2-Dependent Ly6Chigh Monocyte Recruitment to the Lungs and Protects Against Influenza Virus Infection

Bacterial peptidoglycan-derived muramyl dipeptide (MDP) and derivatives have long-recognized antiviral properties but their mechanism of action remains unclear. In recent years, the pattern-recognition receptor NOD2 has been shown to mediate innate responses to MDP. Here, we show that MDP treatment of mice infected with Influenza A virus (IAV) significantly reduces mortality, viral load and pulmonary inflammation in a NOD2-dependent manner. Importantly, the induction of type I interferon (IFN) and CCL2 chemokine was markedly increased in the lungs following MDP treatment and correlated with a NOD2-dependent enhancement in circulating monocytes. Mechanistically, the protective effect of MDP could be explained by the NOD2-dependent transient increase in recruitment of Ly6Chigh “inflammatory” monocytes and, to a lesser extent, neutrophils to the lungs. Indeed, impairment in both Ly6Chigh monocyte recruitment and survival observed in infected Nod2-/- mice treated with MDP was recapitulated in mice deficient for the chemokine receptor CCR2 required for CCL2-mediated Ly6Chigh monocyte migration from the bone marrow into the lungs. MDP-induced pulmonary monocyte recruitment occurred normally in IAV-infected and MDP-treated Ips-1-/- mice. However, IPS-1 was required for improved survival upon MDP treatment. Finally, mycobacterial N-glycolyl MDP was more potent than N-acetyl MDP expressed by most bacteria at reducing viral burden while both forms of MDP restored pulmonary function following IAV challenge. Overall, our work sheds light on the antiviral mechanism of a clinically relevant bacterial-derived compound and identifies the NOD2 pathway as a potential therapeutic target against IAV

Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells

The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17–producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17–producing T cells. These data suggest that IL-12Rβ1– and STAT-3–dependent signals play a key role in the differentiation and/or expansion of human IL-17–producing T cell populations in vivo