Mycobacterium tuberculosis (M.tb), the causative bacterium of pulmonary tuberculosis (TB), is a serious global health concern. Central to M.tb effective immune avoidance is its ability to modulate the early innate inflammatory response and prevent the establishment of adaptive T-cell immunity for nearly three weeks.

When compared with other intracellular bacterial lung pathogens, such as Legionella pneumophila, or even closely related mycobacterial species such as M. smegmatis, this delay is astonishing. Customarily, the alveolar macrophage (AM) acts as a sentinel, detecting and alerting surrounding cells to the presence of an invader. However, in the case of M.tb, this may be impaired, thus delaying the recruitment of antigen-presenting cells (APCs) to the lung. Upon uptake by APC populations, M.tb is able to subvert and delay the processing of antigen, MHC class II loading, and the priming of effector T cell populations.

This delay ultimately results in the deferred recruitment of effector T cells to not only the lung interstitium but also the airway lumen. Therefore, it is of upmost importance to dissect the mechanisms that contribute to the delayed onset of immune responses following M.tb infection. Such knowledge will help design the most effective vaccination strategies against pulmonary TB.

Given the polymicrobial nature of pulmonary infections in patients with cystic fibrosis (CF), it is essential to enhance our knowledge on the composition of the microbial community to improve patient management. In this study, we developed a pyrosequencing approach to extensively explore the diversity and dynamics of fungal and prokaryotic populations in CF lower airways.

METHODOLOGY AND PRINCIPAL FINDINGS: Fungi and bacteria diversity in eight sputum samples collected from four adult CF patients was investigated using conventional microbiological culturing and high-throughput pyrosequencing approach targeting the ITS2 locus and the 16S rDNA gene. The unveiled microbial community structure was compared to the clinical profile of the CF patients.

Pyrosequencing confirmed recently reported bacterial diversity and observed complex fungal communities, in which more than 60% of the species or genera were not detected by cultures. Strikingly, the diversity and species richness of fungal and bacterial communities was significantly lower in patients with decreased lung function and poor clinical status. Values of Chao1 richness estimator were statistically correlated with values of the Shwachman-Kulczycki score, body mass index, forced vital capacity, and forced expiratory volume in 1 s (p = 0.046, 0.047, 0.004, and 0.001, respectively for fungal Chao1 indices, and p = 0.010, 0.047, 0.002, and 0.0003, respectively for bacterial Chao1 values).

Phylogenetic analysis showed high molecular diversities at the sub-species level for the main fungal and bacterial taxa identified in the present study. Anaerobes were isolated with Pseudomonas aeruginosa, which was more likely to be observed in association with Candida albicans than with Aspergillus fumigatus.

CONCLUSIONS: In light of the recent concept of CF lung microbiota, we viewed the microbial community as a unique pathogenic entity. We thus interpreted our results to highlight the potential interactions between microorganisms and the role of fungi in the context of improving survival in CF.

Asthma has several phenotypical features, including recurrent exacerbations and recurrent episodes of upper respiratory infection (URI).

PURPOSE: A retrospective study was performed to identify the characteristics of adult patients with recurrent exacerbations of asthma, especially in association with recurrent episodes of URI.

METHODS: Information was collected using a self-administered questionnaire given to 7070 patients in autumn-winter 2006, 4859 patients in spring-summer 2007, and 4452 patients in autumn-winter 2007. The patients reported the degree of symptoms and the frequency of febrile episodes of URI and exacerbations. Severe exacerbations were defined as a self-report of asthma-related hospitalization, an emergency department visit, or a requirement for systemic corticosteroids. Recurrent febrile URI and exacerbations were defined as two or more episodes within the previous 6 months. A Poisson regression model was used to identify the factors that were predictors of a risk for exacerbations.

RESULTS: Of the 6266 patients who completed the questionnaire, the frequencies of febrile URI and episodes of severe exacerbations were 1.54 and 0.54 per subject per year, respectively. Logistic regression analysis showed that an older age [odds ratio (OR): 1.57; 95% confidence interval (CI): 1.15-2.13], female sex (OR: 1.58; 95% CI: 1.20-2.08), recurrent febrile episodes of URI (OR: 2.68; 95% CI: 1.47-4.91), a history of previous exacerbation within 1 year (OR: 1.74; 95% CI: 1.28-2.34), disuse of inhaled corticosteroids (ICSs) (OR: 2.63; 95% CI: 1.68-4.12), and disuse of add-on leukotriene receptor antagonists (LTRAs) (OR: 1.42; 95% CI: 1.06-1.74) were independently associated with moderate to severe symptom-severity. Poisson regression analysis showed that the independent factors that contributed to the frequency of recurrent severe exacerbations were female sex (regression coefficient β = 0.62, p < .01), an episode of sputum with coughing (β = 1.23, p < .01), nocturnal awakening (β = 1.22, p < .01), and severe exacerbation (β = 0.78, p < .01) within the previous 6 months.

CONCLUSION: Symptom-severity of asthma and the frequency of severe exacerbations were associated with previous exacerbations and susceptibility to URI.