Exposure to silica dust may trigger pulmonary fibrosis in human and mouse cells, study indicates

By Dr Deepu

Researchers found in “both human cells and mice” that “exposure to silica dust may trigger pulmonary fibrosis (PF) because silica particles block a self-cleansing process used by cells, termed autophagy, which drives cell death in the lungs.”

The researchers have summarized their study by saying” we have shown that autophagy participates in SiNPs-induced PF. We have also identified that the autophagic flux blockage results from lysosomal acidification inhibition, which then triggers apoptosis in AECs and subsequent PF. These findings provide a new mechanism by which SiNPs trigger PF by targeting AECs. Furthermore, these results may lead to new strategies to prevent SiNPs-induced PF by enhancing autophagic degradation”.

The findings were published in Cell Death & Disease.

One-year treatment with cyclophosphamide tied to short-term improvements in patients with symptomatic systemic sclerosis-related interstitial lung disease, study indicates

By Dr Deepu

Researchers found that “in patients with symptomatic systemic sclerosis (SSc)-related interstitial lung disease (ILD), 1-year treatment with the immunosuppressant cyclophosphamide (CYC) is associated with short-term improvements in forced vital capacity (FVC)%-predicted and the modified Rodnan skin score (mRSS), but not in the diffusing capacity of the lungs for carbon monoxide (DLCO)%-predicted.”

Participants enrolled in the CYC arms of SLS I (n = 79) and II (n = 69) were included in the study. SLS I and II randomized participants to oral CYC for 1 year and followed patients for an additional year off therapy (in SLS II, patients received placebo in Year 2). Outcomes included the forced vital capacity (FVC%)-predicted and DLCO%-predicted (measured every 3 months) and quantitative radiographic extent of interstitial lung disease (measured at 1 and 2 yearsrs for SLS I and SLS II, respectively). Joint models were created to evaluate the treatment effect on the course of the FVC/DLCO over 2 years while controlling for baseline disease severity.

Researchers found that SLS I and II CYC participants had similar baseline characteristics. After adjusting for baseline disease severity, there was no difference in the course of the FVC%-predicted (p = 0.535) nor the DLCO%-predicted (p = 0.172) between the SLS I and II CYC arms. In both groups, treatment with CYC led to a significant improvement in the FVC%-predicted from 3 to 12 months, but no significant improvement beyond this point. Treatment with CYC had no effect on the DLCO for either group.

Finally they could conclude that Treatment with 1 year of oral CYC led to similar improvements in lung function in both SLS I and II, although the effects were not sustained following cessation of CYC. These results suggest that increasing the duration of ILD therapy may improve outcomes for patients with systemic sclerosis–ILD.

The findings were published in the Journal of Rheumatology.

People who receive flu vaccine while hospitalized no more likely to require extra care than inpatients who are not vaccinated, suggests a large study

By Dr Deepu

 In a recent study, the researchers evaluated the risk of outcomes of interest between those who received influenza vaccination during their hospitalization vs those who were never vaccinated that season or were vaccinated at other times using propensity score analyses with inverse probability of treatment weighting. Outcomes of interest included rates of outpatient and emergency department visits, readmissions, fever, and clinical laboratory evaluations for infection (urine, blood, and wound culture; complete blood cell count) in the 7 days following discharge. Data on 290,149 US hospitalizations involving 255,737 patients over three consecutive flu seasons has suggested that patients who receive the flu vaccine while hospitalized are no more likely to develop fever or require extra doctor or hospital visits after they go home than inpatients who don’t get vaccinated. The author's have concluded that findings provide reassurance about the safety of influenza vaccination during hospitalization. Every contact with a health care professional, including during a hospitalization, is an opportunity to vaccinate. The findings were published in Mayo Clinic Proceedings.

Research looks into COPD risk among never-smokers

By Dr Deepu

Data from the years 2012-2015 was pulled from the National Health Interview Survey (NHIS), a cross-sectional household survey conducted annually by the National Center for Health Statistics (NCHS). All subjects were aged 40 years or older and self-reported a COPD diagnosis.
Urbanization was evaluated using the 2013 NCHS Urban-Rural Classification that divides counties into 6 categories: large metro, central (urban); large metro, fringe( suburban); medium metro; small metro, micropolitan (rural), and non-core (rural).
The American Community Survey was used to collect information about environmental exposures at the census level that may increase COPD risk, including poverty, jobs associated with developing lung disease, and household heating sources. Census tracts were divided into poor and non-poor, based on whether 20% of households were living below poverty line.
Never-smokers were defined as those that smoked less than 100 cigarettes in their lifetime; smoking exposure was appraised by the number of smoking years per participant.
Of the 90,334 subjects, 14.9% lived in rural counties, and 15.7% lived in poor census tracts. Almost half were current or former smokers (43.9%), while 23.2% were never-smokers. Among the current or former smokers, 13.5% had COPD and 4.3% of never-smokers had COPD.
Rural regions had the highest prevalence of COPD (12.7%). Within those areas, the rural poor had the highest occurrence of COPD (15.7%), compared to 12% in rural non-poor communities. Non-poor urban communities had the lowest prevalence of COPD (6.1%).
Living in a rural census tract predicted COPD even after adjusting for residence, age, sex, race, smoking status, household wealth, education, community poverty, health insurance, and solid fuel use. The association was the same among never-smokers (OR 1.34, p<.001) and current or former smokers (OR 1.19, p .031).
Poverty increased the chances of COPD by 8%, while wealth (including college education) and home ownership lowered those chances.

For never-smokers, there was a strong link between using coal as a fuel source and developing COPD, increasing the odds by 9%.
The study demonstrates the high burden of COPD in poor, rural communities and gives insight into the role that environmental exposures—including heating with coal—play in COPD development.
However, some of this is changing. The COPD Foundation and the National Institutes of Health (NIH) COPD National Action Plan are beginning to focus efforts on improving care and building a research infrastructure for patients with COPD in rural areas. McCormack’s research group at JHU has partnered with Eastern Tennessee State University to launch a study focused on understanding the impact of household air pollution on individuals living with COPD in Appalachia.
The study, “Rural Residence and Poverty are Independent Risk Factors for COPD in the United States”, was published on November 2, 2018, in the American Thoracic Society’s American Journal of Respiratory and Critical Care.

Absence of Alveolar Neutrophilia Predictive of Negative Bacterial Pneumonia

By Dr Deepu

Results of a study published in the American Journal of Respiratory and Critical Care Medicine has revealed that  Patients undergoing evaluation for ventilator-associated pneumonia who had an alveolar neutrophil percentage <50% had a negative predictive value >90% for bacterial pneumonia.
Bronchoalveolar lavage specimens from patients undergoing evaluation for ventilator-associated pneumonia at an urban academic medical center were analyzed retrospectively for associations between alveolar neutrophilia and bacterial pneumonia diagnosis. All lavage samples were processed for flow-cytometry sorting within 12 hours of collection. Pneumonia was defined as ≥104 colony-forming units/mL of a bacterial species on quantitative culture in the setting of a clinical suspicion of infection and an abnormal chest radiograph.
Of the 1156 bronchoalveolar lavage specimens screened for inclusion, 851 were included in the final analysis. Of these 851 specimens, 344 (40.4%) met the definition for bacterial pneumonia. The most common pathogens isolated were Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Klebsiella pneumoniae. The area under the curve for bronchoalveolar lavage neutrophilia was 0.751 (95% CI, 0.719-0.784). When bronchoalveolar lavage neutrophils were <50%, the negative predictive value for pneumonia was 91.5%.
 the researchers concluded The absence of alveolar neutrophilia is useful in ruling out bacterial pneumonia in mechanically ventilated patients with suspected infection. A combination of cellular and molecular analysis of the host and pathogen in [bronchoalveolar lavage] fluid shows promise for improving the diagnosis and management of pneumonia.

Original article reference
Walter J, Ren Z, Yacoub T, et al. Multidimensional assessment of the host response in mechanically ventilated patients with suspected pneumonia [published online November 6, 2018]. Am J Respir Crit Care Med. doi:10.1164/rccm.201804-0650OC