To evaluate the performance of an algorithm based on WHO recommendations for diagnosis of smear-negative pulmonary tuberculosis in HIV-negative patients.

Methods  We recruited HIV-negative patients with clinical suspicion of tuberculosis who had had three negative sputum smears in Lima, Peru. All included subjects underwent a complete anamnesis, physical examination and chest X-ray, and had a sputum specimen cultured in Ogawa, Middlebrook 7H9 media and MGIT®. We applied an algorithm based on WHO recommendations to classify patients as having tuberculosis or not. The diagnostic performance of the algorithm was evaluated comparing its results against the reference standard of a positive culture for M. tuberculosis in either of the media used.

Results  A total of 264 of the 285 patients included (92.6%) completed evaluation and follow up. Of these, 70 (26.5%) had a positive culture for M. tuberculosis. Clinical response to a broad spectrum course of antibiotics was good in 32 of these 70 patients (45.7; 95%CI 34.0-57.4%). Overall, the algorithm attained a sensitivity of 22.9% (95% CI 13.1-32.7%) and a specificity of 95.4 % (95% CI 92.4-98.3%) compared to culture results. The positive likelihood ratio was 4.93 and the negative likelihood ratio was 0.81.

Conclusions  The sensitivity and negative likelihood ratio of the algorithm is poor. It should be re-evaluated, and possibly adapted to local circumstances before further use. The clinical response to an antibiotic trial is the most important component to reassess. We also suggest considering performing chest X-ray earlier in the diagnostic work-up.

Sarcoidosis, a systemic granulomatous disease of undetermined etiology, is characterized by a variable clinical presentation and course. During the past decade, advances have been made in the study of sarcoidosis.

The multicenter ACCESS (A Case Control Etiologic Study of Sarcoidosis) trial recruited > 700 subjects with newly diagnosed sarcoidosis and matched control subjects. Investigators were unable to identify a single cause of sarcoidosis, but ACCESS paved the way for subsequent etiologic studies. The Mycobacterium tuberculosis catalase-peroxidase protein has been identified as a potential sarcoidosis antigen. Genetic aspects of the disease have been elucidated further. Genome-wide scans have identified candidate genes. Gene expression analyses have defined cytokine dysregulation in sarcoidosis more clearly. Although the criteria for diagnosis have not changed, sarcoidosis remains a diagnosis of exclusion best supported by a tissue biopsy specimen that demonstrates noncaseating granulomas in a patient with compatible clinical and radiologic features of the disease. Endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated diagnosis, often eliminating the need for more invasive procedures, such as mediastinoscopy. PET scanning has proven valuable in locating occult sites of active disease.

Currently, no reliable prognostic biomarkers have been identified. The tumor necrosis factor inhibitors, a relatively new class of agents, have been used in patients with refractory disease. It is unclear whether phosphodiesterase-5 inhibitors, prostaglandin analogs, or endothelin antagonists should be used for the treatment of sarcoidosis-associated pulmonary hypertension.

Pseudomonas aeruginosa (Pa) is associated with poor pulmonary outcomes in cystic fibrosis (CF), but the association between age of Pa infection and severity of subsequent lung disease has not been thoroughly investigated.

OBJECTIVE: Our goal was to determine the association between age of Pa acquisition and subsequent severity of CF lung disease.

METHODS: Case-control study using CF Foundation Registry data of 629 ΔF508 homozygotes with severe and mild lung disease (FEV(1) in the lowest and highest quartile of birth cohort, respectively). Multivariate logistic regression was performed to determine the association between age of Pa acquisition and lung disease severity.

RESULTS: Earlier age of Pa infection was strongly associated with increased odds of severe lung disease. For first and persistent Pa, adjusted odds ratios for severe lung disease were 6.5 (95% CI 3.1, 13.7; P < 0.0001) and 11.2 (5.4, 23.1; P < 0.0001), respectively, for subjects with infection before age 5 versus at ≥10 years; the association was stronger in females than males.

CONCLUSIONS: Earlier Pa infection, particularly before 5 years of age, is strongly associated with severe CF lung disease later in life. This study is not designed to determine causality; Pa infection may be causing lung injury, or may be a marker of ongoing inflammation and lung damage in young children with CF. Pediatr. Pulmonol. © 2011 Wiley-Liss, Inc.

Chlamydia pneumoniae (C. pneumoniae) is a common cause of acute respiratory infection and has been hypothesised to cause several chronic diseases, including lung cancer. Numbers studies were conducted to analyse the association between C. pneumoniae infection and risk of lung cancer, but no clear consensus had been found. To assess this relationship more precisely, a meta-analysis was performed.

The electronic databases PubMed, Embase, Web of Science and CNKI were searched; Data were extracted and analysed independently by two investigators. Ultimately, 12 studies, involving 2595 lung cancer cases and 2585 controls from four prospective studies and eight retrospective studies were included. Overall, people exposed to C. pneumoniae infection had an odds ratio (OR) of 1.48 (95% confidence interval (CI), 1.32-1.67) for lung cancer risk, relative to those not exposed. C. pneumoniae infection was clearly identified as a risk factor for lung cancer in both prospective studies (OR, 1.16; 95% CI, 1.00-1.36) and retrospective studies (OR, 2.17; 95% CI, 1.79-2.63) and in both IgA⩾16 cutoff group (OR, 1.22; 95% CI, 1.06-1.41) and the IgA⩾64 cutoff group (OR, 2.35; 95% CI, 1.88-2.93).

In conclusion, C. pneumoniae infection is associated with an increased risk for lung cancer, higher titre may be a better predictor of lung cancer risk.