Fibrotic interstitial pneumonias are a group of rare diseases characterised by distortion of lung interstitium. Patients with mutations in surfactant-processing genes, such as surfactant protein C (SFTPC), surfactant protein A1 and A2 (SFTPA1andA2), ATP binding cassette A3 (ABCA3) and Hermansky–Pudlak syndrome (HPS1,2and4), develop progressive pulmonary fibrosis, often culminating in fatal respiratory insufficiency. Although many mutations have been described, little is known about the optimal treatment strategy for fibrotic interstitial pneumonia patients with surfactant-processing mutations.We performed a systematic literature review of studies that described a drug effect in patients, cell or mouse models with a surfactant-processing mutation. In total, 73 articles were selected, consisting of 55 interstitial lung disease case reports/series, two clinical trials and 16 cell or mouse studies. Clinical effect parameters included lung function, radiological characteristics and clinical symptoms, while experimental outcome parameters included chemokine/cytokine expression, surfactant trafficking, necrosis and apoptosis. SP600125, a c-jun N-terminal kinase (JNK) inhibitor, hydroxychloroquine and 4-phenylbutyric acid were most frequently studied in disease models and lead to variable outcomes, suggesting that outcome is mutation dependent.This systematic review summarises effect parameters for future studies on surfactant-processing disorders in disease models and provides directions for future trials in affected patients.

Lung transplant patients are immunocompromised because of the medication they receive to prevent rejection, and as a consequence are susceptible to (respiratory) infections. Adequate vaccination st...

Background: Community-acquired pneumonia (CAP) is a frequent cause of death worldwide, and in sub-Saharan Africa particularly. Human immunodeficiency virus infection (HIV) and tuberculosis (TB) influence pathogen distribution in patients with CAP. Previous studies in sub-Saharan Africa have shown different frequencies of respiratory pathogens and antibiotic susceptibility compared to studies outside Africa. This study aimed to investigate the aetiology, presentation, and treatment outcomes of community-acquired pneumonia in adults at the University Teaching Hospital in Lusaka, Zambia. Materials and methods: Three-hundred-and-twenty-seven patients were enrolled at the University Teaching Hospital in Lusaka between March 2018 and December 2018. Clinical characteristics and laboratory data were collected. Sputum samples were tested by microscopy, other TB diagnostics, and bacterial cultures. Results: The commonest presenting complaint was cough (96%), followed by chest pain (60.6%), fever (59.3%), and breathlessness (58.4%). The most common finding on auscultation of the lungs was chest crackles (51.7%). Seventy percent of the study participants had complaints lasting at least a week before enrolment. The prevalence of HIV was 71%. Sputum samples were tested for 286 patients. The diagnostic yield was 59%. The most common isolate was Mycobacterium tuberculosis (20%), followed by Candida species (18%), Klebsiella pneumoniae (12%), and Pseudomonas aeruginosa (7%). Streptococcus pneumoniae was isolated in only four patients. There were no statistically significant differences between the rates of specific pathogens identified in HIV-infected patients compared with the HIV-uninfected. Thirty-day mortality was 30%. Patients with TB had higher 30-day mortality than patients without TB (p = 0.047). Conclusion: Mycobacterium tuberculosis was the most common cause of CAP isolated in adults at the University Teaching Hospital in Lusaka, Zambia. Gram-negative organisms were frequently isolated. A high mortality rate was observed, as 30% of the followed-up study population had died after 30 days.

Background: Telomere dysfunction can underly the development of idiopathic pulmonary fibrosis (IPF), and recent work suggests that patients with telomere syndromes might benefit from treatment with androgens, such as danazol.Methods: This was a prospective observational cohort study. 50 patients with IPF received off-label treatment with danazol after they showed progressive disease under treatment with pirfenidone or nintedanib. The primary outcome was the difference in yearly decline in forced vital capacity (FVC) prior to (pre) and after (post) start of treatment with danazol.Results: There was no significant difference in FVC-decline between 1 year pre and 1 year post start of danazol treatment (mean decline pre 395 mL (95% confidence interval (CI) 290–500) compared to post 461 mL (95% CI 259–712); p=0.46; paired t-test). 11 patients (22%) were still on danazol after 1 year, and 39 patients had stopped danazol, mainly because of side-effects (56%) or death (33%). In patients who were still using danazol after 1 year, FVC-decline significantly slowed down under danazol treatment (mean pre 512 mL (95% CI 308–716)versuspost 198 mL (95% CI 16–380); p=0.04). Median survival post danazol was 14.9 months (95% CI 11.0–18.8).Conclusion: Danazol as a treatment of last resort in patients with IPF did not lead to slowing of lung function decline and was associated with significant side-effects. It remains to be determined if earlier treatment or treatment of specific patient subgroups is beneficial.

Background. Diabetes mellitus (DM) is known to be associated with active tuberculosis (TB). Zambia is a low-income sub-Saharan African country with a high TB burden and increasing numbers of newly diagnosed DM patients. Materials and Methods. This was an observational study conducted at the University Teaching Hospital in Lusaka, Zambia, from October 2014 to February 2016. Adult patients with active TB were screened for DM. Results. A total of 127 individuals were enrolled in the study. Six patients (5%) were found to have diabetes. Of these, three had a prior diagnosis of diabetes and were on medication while three were newly diagnosed. Low education level was significantly associated with DM (p=0.001; 95% CI 0.001–0.148). Conclusion. The prevalence of DM among individuals with smear positive TB in our study population was similar to that of the general population in Zambia.