This study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.

Objectives There are epidemiological studies indicating that exposure to metal fumes is a risk factor for infectious pneumonia. Whether occupational exposure to other agents, such as inorganic dust or chemicals, also increases the risk for infectious pneumonia is not clear. The aim of the present study was to elucidate whether occupational exposure to respiratory pollutants and irritants increases the risk for infectious pneumonia. Design Prospective cohort study. Setting Swedish male construction workers. Participants 320 143 male construction workers exposed to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), wood dust, metal fumes and chemicals (organic solvents, diisocyanates and epoxi resins) or unexposed. Main outcome measures The cohort was followed from 1971 to 2003 and the main outcome measures were mortality to infectious pneumonia, lobar pneumonia or pneumococcal pneumonia. RRs were obtained by the person-years method and from Poisson regression models, adjusting for baseline values of age and smoking habits. Results Among men aged 20e64 years there was increased mortality from infectious pneumonias among construction workers exposed to metal fumes (RR 2.31, 95% CI 1.35 to 3.95), inorganic dust (RR 1.87, 95% CI 1.22 to 2.87) and chemicals (RR 1.91, 95% CI 1.37 to 3.22). The mortality was also increased from both lobar pneumonia and pneumococcal pneumonia. Among men aged 65e84 years the occupational exposure to inorganic dust and chemicals was associated with slightly increased mortality from infectious pneumonia. Among groups with mutually exclusive exposures there was increased mortality from infectious pneumonias among construction workers exposed to inorganic dust, but not among those exposed to wood dust or chemicals. There were no cases among workers exposed only to metal fumes. Conclusions Our findings indicate that exposure to inorganic dust increases the mortality from infectious pneumonias, especially lobar pneumonia and pneumococcal pneumonia. The mechanism is unclear, but the effect may be mediated through induced airways inflammation.

Background: Bacterial adherence to mucosal and epithelial cell structures is of importance for the persistence of bacteria in the airways. Cigarette smoking and chronic bronchitis are associated with increased bacterial adherence. N-Acetylcysteine (NAC) medication reduces the number of infectious exacerbations in patients with chronic bronchitis, and NAC medication has been associated with low intrabronchial bacterial numbers. Objective: We investigated whether NAC influences bacterial adherence as a possible mechanism behind its clinical effects. Methods: Highly adhering test strains of Streptococcus pneumoniae and Haemophilus influenzae were used to investigate the influence of four pharmacological compounds on adherence to oropharyngeal epithelial cells in vitro. Adhesion assays were performed both during short-term exposure to, as well as after long-time incubation with, NAC, lidocaine, hydrocortisone and terbutaline at concentrations not inhibiting bacterial growth. Results: Only NAC showed a significant inhibitory effect on adhesion of H. influenzae during short-term incubation. After long-term incubation, both NAC and hydrocortisone inhibited bacterial adhesion for both strains in a dose-dependent manner. When NAC’s effect on three different strains of S. pneumoniae and four strains of H. influenzae was studied, inhibition of bacterial adhesion was found for three strains of each species. Conclusions: NAC lowers bacterial adhesion in vitro to oropharyngeal epithelial cells in doses equivalent to that is being used clinically. This effect might be a contributory mechanism behind the reduction of infectious exacerbations in chronic bronchitis patients.

Previous studies on mouse models have indicated that interleukin (IL)-17 and IL-17-producing T-helper (Th) cells are important for pulmonary host defence against Gram-negative bacteria. Human correlates to these findings have not yet been demonstrated. The aim of the present study was to determine whether or not IL-17-producing Th cells are present and whether IL-17 and other Th17-associated cytokines are involved in the immunological response to endotoxin in human airways.Segmental exposure to endotoxin and contralateral exposure to vehicle were performed in the lungs of healthy volunteers, with subsequent bronchoalveolar lavage 12 or 24 h after exposure to study local changes in cytokines and inflammatory cells.Endotoxin exposure increased concentrations of IL-17, IL-22 and their downstream effector molecules, human b-defensin-2 and IL-8/CXC chemokine ligand 8, in bronchoalveolar lavage fluid. Th cells with the capacity to produce IL-17 were found among the bronchoalveolar lavage cells, and expression of IL-17 mRNA correlated with expression of the transcription factor, retinoic-acidreceptor-related orphan receptor C variant 2. Moreover, endotoxin increased the numbers of neutrophils, macrophages and IL-17-producing T-cells, as well as the concentration of the Th17-regulating cytokines, IL-21 and IL-23.In conclusion, IL-17-producing Th cells are present, and IL-17, as well as other Th17-associated cytokines, is involved in the immunological response to endotoxin in human airways.

ObjectivesOccupational exposures to metal fumes have been associated with increased pneumonia risk, but the risk of invasive pneumococcal disease (IPD) has not been characterised previously.MethodsWe studied 4438 cases aged 20–65 from a Swedish registry of invasive infection caused by Streptococcus pneumoniae. The case index date was the date the infection was diagnosed. Six controls for each case, matched for gender, age and region of residency, were selected from the Swedish population registry. Each control was assigned the index date of their corresponding case to define the study observation period. We linked cases and controls to the Swedish registries for socioeconomic status (SES), occupational history and hospital discharge. We applied a job–exposure matrix to characterise occupational exposures. We used conditional logistic analyses, adjusted for comorbidities and SES, to estimate the OR of IPD and the subgroup pneumonia–IPD, associated with selected occupations and exposures in the year preceding the index date.ResultsWelders manifested increased risk of IPD (OR 2.99, 95% CI 2.09 to 4.30). Occupational exposures to fumes and silica dust were associated with elevated odds of IPD (OR 1.11, 95% CI 1.01 to 1.21 and OR 1.33, 95% CI 1.11 to 1.58, respectively). Risk associated with IPD with pneumonia followed a similar pattern with the highest occupational odds observed among welders and among silica dust exposed.ConclusionWork specifically as a welder, but also occupational exposures more broadly, increase the odds for IPD. Welders, and potentially others with relevant exposures, should be offered pneumococcal vaccination.