HRCT findings in various ILDs

By Dr Deepu
Here is an easy pictorial representation of the various ILD.

Anti-malondialdehyde-acetaldehyde adducts antibodies in lung tissues may play important role in pathogenesis of RA-associated interstitial lung disease, study indicates

By Dr Deepu

Anti-malondialdehyde-acetaldehyde adducts (MAA) antibodies and MAA expression in lung tissues of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) likely play an important role in RA-ILD pathogenesis, and anti-MAA antibodies may function well as serum biomarkers in the identification of this disease manifestation.
Patients with RA face premature mortality and RA-ILD is a major determinant of worse long-term outcomes, with a median survival as short as 3 years after diagnosis. In the present study, researchers compared serum anti-MAA antibodies and MAA expression in lung tissues of patients from 13 sites fulfilling the 1987 American College of Rheumatology criteria by selecting participants from the Veterans Affairs Rheumatoid Arthritis Registry.
Multivariable logistic regression models were used to assess the association between anti-MAA antibodies (immunoglobulins A, M, and G [IgA, IgM, IgG]) and RA-ILD status by combining RA alone with RA+chronic obstructive pulmonary disease (COPD) for a comparator group, as unadjusted comparisons found no significant differences in concentrations of anti-MAA antibodies between these groups. Lung tissues from RA-ILD patients, and other patients with ILD, emphysema, and controls were stained for MAA, macrophages (CD68), citrulline, B cells (CD19/CD27), T cells (CD3), and extracellular matrix proteins (fibronectin, vimentin, type-II collagen). Lung tissue expression and MAA co-localization were quantified and compared.
Among the total 1823 participants with RA, 90 had RA-ILD. Higher serum concentrations of IgM and IgA anti-MAA antibodies were seen in RA-ILD vs RA+COPD or RA alone (P =.005). After adjustment for covariates, the highest quartiles of IgM (odds ratio [OR] 2.23; 95% CI, 1.19-4.15) and IgA (OR 2.09; 95% CI, 1.11-3.90) anti-MAA antibody were significantly associated with RA-ILD. MAA expression in lung tissue was greater in RA-ILD than all other groups (P  <.001). The RA-ILD group also showed the greatest degree of MAA co-localized with CD19+ B cells (r =0.78), citrulline (r =0.79), and extracellular matrix proteins (type-II collagen [r =0.72] and vimentin [r =0.77]).
The study authors concluded the study by noting "These findings suggest that MAA immune responses could play an important role in the pathogenesis of RA-ILD and anti-MAA antibodies may be promising serum biomarkers in the identification of this extra-articular disease manifestation"
The finding were published in arthritis and rheumatology

Many children with asthma do not use inhalers properly, study indicates

By Dr Deepu

Research indicates “many children with asthma don’t use their inhalers properly and don’t get a full dose of medicine.” Investigators looked at “inhaler use among 113 children between the ages of 2 and 16 who were hospitalized for asthma.” The researchers found that “at least one crucial step in inhaler technique was missed by 42% of the children,” and approximately “18% did not use a spacer device with their inhaler.” The findings were published in the Journal of Hospital Medicine.

Tuberculosis could be eliminated by 2045, researchers suggest

By Dr Deepu


A new study by researchers  suggests that “increased investment in evidence-based interventions to diagnose, treat, and prevent tuberculosis (TB), especially in high-burden countries, could help end TB” by the year 2045. These interventions should not only “be scaled up, but greater investment and research is needed to develop new methods of diagnosis, treatment, and prevention around the world, [researchers] reported.” Additionally, they suggest that “responsibility for investing in TB programs should be shared between domestic allocation in these countries, as well as external funding through increased developmental assistance.”
The authors mentioned that”to reach these goals, global investment in TB research and development will need to increase to at least $2 billion per year during the next 4 years”.
With the goals of treating 40 million people and preventing 30 million new cases from 2018-2022, the United Nations held its first-ever "high-level meeting" about TB,in September 2018
A TB-free world is possible by 2045 if "increased political will and financial resources" are targeted towards areas where they are needed most, as stated in the report
 In India, the country with the highest burden of TB,  "unavoidable tuberculosis deaths" will cost the country at least $32 billion each year over the next 30 years, even with "optimal implementation of existing tools." The authors also have mentioned that the savings from averting a TB death can be three times the costs in certain countries.
Tuberculosis was declared a global emergency by WHO in 1993. Then, about a third of the world’s population was infected with the bacteria that cause tuberculosis, and the disease was responsible for an estimated 3 million deaths each year. Today, around a quarter of the world’s population has a tuberculosis infection, which causes about 1·6 million annual deaths, making it the leading infectious killer of our time. Although progress has been made in reducing the global burden of tuberculosis in the past 25 years, it has occurred at a frustratingly slow rate. Declines in tuberculosis mortality are not keeping pace with reductions in deaths from other infectious diseases of global importance such as HIV and malaria, and the world is not on track to meet targets set out in the Sustainable Development Goals and the WHO End TB Strategy.
The findings were published in The Lancet.

Statins in Asthma COPD overlap may bring down the risk of CAD and stroke risk

By Dr Deepu

Recently published study in atherosclerosis journal has found that the risk for CAD was lower in all statin-treated patients with ACOS. Whereas the risk for ischemic stroke was lower only in long-term statin users with ACOS. There was no link  between risk for hemorrhagic stroke and  statin use.
A retrospective cohort study was conducted using data from the Longitudinal Health Insurance Database, which included 1 million enrollees in the Taiwan National Health Insurance program from January 1, 2000, through December 31, 2011.
Patients ≥20 years of age with ACOS who were treated with statins (n=916) and those who did not receive statin therapy (n=6338) were enrolled in the study. Investigators examined the cumulative incidence of CAD and stroke (both ischemic and hemorrhagic) with the use of time-dependent Cox proportional regression. Following adjustments for age, sex, inhaled corticosteroid use, oral steroid use, and comorbidities, adjusted hazard ratios (aHRs) and 95% CIs for CAD or stroke in statin users (long-term statin use: >600 days; short-term statin use: ≤600 days) were compared with these values in statin nonusers.
In statin users, the aHRs for CAD and stroke were 0.50 (95% CI, 0.41-0.62) and 0.83 (95% CI, 0.63-1.09), respectively. Furthermore, aHRs for ischemic and hemorrhagic stroke were 0.30 (95% CI, 0.09-0.99) and 0.90 (95% CI, 0.68-1.20), respectively. In addition, in long-term statin users, aHRs for CAD and stroke were 0.23 (95% CI, 0.13-0.41) and 0.42 (95% CI, 0.19-0.89), respectively. In short-term statin users, aHRs for CAD and stroke were 0.58 (95% CI, 0.47-0.71) and 0.93 (95% CI, 0.70-1.23), respectively.
A major limitation of the current study is that lipid levels were not taken into account. Moreover, although a new-user study design was employed, with propensity score matching and a time-dependent model for analysis, results were not as accurate as those derived from randomized controlled trials.

The study was published in atherosclerosis journal

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

Flu shot can save heart failure patients’ lives- study suggests

By Dr Deepu
Getting an annual flu shot can save heart failure patients’ lives, according to new research in the American Heart Association’s journal Circulation.
Flu season usually begins in the fall and runs through the spring, with cases often peaking during the winter months. Annual flu vaccination is regarded as a safe, low-cost way to reduce flu-related deaths and complications and is routinely recommended for patients with histories of heart disease and stroke. However, little is known about the possible impact a simple flu shot may have on the survival of heart failure patients.

Influenza can be very serious or even fatal for patients with heart failure because heart failure patients are often older than 65, have compromised circulation and other health complications, and infection may exacerbate heart failure symptoms. Moreover, heart failure is expected to increase over the next decade as the population ages, highlighting a greater need to provide better care for these patients.
In this study, researchers analyzed data on 134,048 patients with newly diagnosed heart failure over a 12-year period. Flu vaccination rates ranged from 16% in 2003 to 52% in 2015 with a peak of 54% in 2009. Among the researchers’ findings:
Flu vaccination was associated with an 18% reduced risk of premature death, even after accounting for other factors such as medications, other health conditions, income and education
Annual flu vaccination following a heart failure diagnosis was associated with a 19% reduction in both all-cause and cardiovascular death when compared with no vaccination.
Flu vaccination frequency mattered; getting a flu shot less than once per year but more than not at all was associated with a 13% reduced risk of all-cause death and an 8% reduced risk of cardiovascular death.
Timing mattered; there was a greater reduction in cardiovascular and all-cause death when vaccination occurred earlier in the flu season during September and October vs in November and December.
Read free access original study in AHA journal website

Blood Decorin Levels May Serve as Prognostic Marker for IPF Patients After Acute Exacerbation, Study Suggests

By Dr Deepu
A new research has suggested Reduced levels of decorin proteins in the blood may be linked to a lower risk of death among patients with idiopathic pulmonary fibrosis (IPF) who have experienced acute exacerbations. “Serum decorin is a potential prognostic biomarker in patients with acute exacerbation of idiopathic pulmonary fibrosis,” published in the Journal of Thoracic Diseases has shed light on the topic. Acute worsening of respiratory function, also known as acute exacerbations, can have a significant negative impact on the clinical outcome of patients with IPF. These acute events have been reported to occur in about 8.6% of IPF cases one year after diagnosis, increasing to 23.9% three years after diagnosis. After the onset of acute exacerbations, the death rate of IPF patients is about 50%. This high mortality rate highlights the importance of recognizing risk factors that could contribute to the development of these acute events to ensure adequate prevention. Researchers have now evaluated the role of the decorin protein in the development and progression of acute exacerbations in patients with IPF and idiopathic interstitial pneumonia (IIP), which is also a fibrotic lung disease. Decorin is known to regulate inflammation and wound healing. In IPF, decorin can be found at fibrotic lesions and was shown to prevent lung fibrosis in mice. This protein was also shown to inhibit collagen production by fibroblasts, which is a key mechanism in fibrosis progression. The team evaluated the levels of decorin in blood samples collected from 21 IPF patients, 35 patients with IIP (other than IPF) who were hospitalized due to acute exacerbations, and 36 healthy volunteers. They also evaluated the protein levels in 97 patients who had stable IIP (no disease exacerbations). Researchers found that IIP patients who had acute exacerbations had reduced levels of decorin by about 23.8% (7,183.8 vs. 9,430.2 ng/mL), compared with stable IIP patients, and 35.7% (7,183.8 vs. 11,171.9 ng/mL), compared with healthy controls. The team also compared the levels of decorin in 34 IIP patients between when they were clinically stable and during an acute exacerbation period. The analysis showed that blood decorin levels were significantly lower during an acute exacerbation than in the clinically stable phase in IPF patients, with a mean reduction of about 21.4% (6,894.5 vs. 8,778.5 ng/mL). However, this difference was not found in the non-IPF patient subgroup. Further analysis failed to find any correlation between blood decorin levels and any clinical parameter after hospital admission due to acute exacerbation, including blood laboratory results, SIRS score, and APACHE II score — two commonly used prognostic measures. Overall, the survival rate 60 days after hospital admission was 53.6% in IIP patients. Comparison of mean decorin levels between survivors and non-survivors did not reveal a significant difference. However, when the team divided IPF patients into high and low blood decorin groups — using median decorin level as a reference — the survival rate was significantly higher in patients with low decorin levels than in those with high levels. Still, the team could not find any significant differences in clinical parameters except PF ratio, which is the arterial partial pressure of carbon dioxide/fraction of inspiratory oxygen ratio, a measure of respiratory function. Overall, the team found that “decorin levels were lower in IIP patients than in HVs [healthy volunteers], and decreased during AE [acute exacerbation];” that “decorin levels during AE were not correlated with any clinical characteristics except for PF ratio in IPF patients; and [that] “IPF patients with lower serum decorin levels had better prognosis than those with higher levels after the onset of AE.” Based on these results, the team believes that “[blood] decorin level is a potential prognostic biomarker after the onset of acute exacerbations in patients with IPF.” Still, additional studies are necessary to clarify the role of decorin in the underlying mechanisms of both IPF and IIP

Exercise Training May Improve Daily Life For Obese Individuals With Asthma, Study Suggests

By Dr Deepu

Obese adults with asthma have an increased number of comorbidities and reduced daily life physical activity (DLPA), which may worsen asthma symptoms. Exercise is recommended to improve asthma outcomes; however, the benefits of exercise for psychosocial comorbidities and physical activity levels in obese adults with asthma have been poorly investigated.
The objective of the study was assess the effects of exercise on DLPA, asthma symptoms and psychosocial comorbidities in obese adults with asthma. The study included  Fifty-five grade II obese adults with asthma, the study subjects were randomly assigned to either a weight-loss program+exercise program (WL+E group, n=28) or a weight loss program +sham (WL+S group, n=27). The WL+E group incorporated aerobic and resistance muscle training into the weight-loss program (nutrition and psychological therapies), while the WL+S group performed breathing and stretching exercises. DLPA, asthma symptoms, sleep quality and anxiety and  depression  symptoms were quantified before and after treatment.
The results obtained after 3 months were positive, the WL+E group presented a significant increase in daily step counts (3,068 ± 2,325 vs. 729 ± 1,118 steps/day) and the number of asthma-symptom-free days (14.5 ± 9.6 vs. 8.6 ± 11.4 d/mo) compared with the WL+S group. The proportion of participants with improvements in depression symptoms (76.4 vs. 16.6 %) and a lower risk of developing obstructive sleepapnea (56.5 vs. 16.3%) was greater in the WL+E group than in the WL+S group (P<0.05). Significant improvements in sleep efficiency (6.6 ± 5.1 vs. 1.3 ± 4.7%) and latency (-3.7 ± 5.9 vs. 0.2 ± 5.6 min) were also observed in the WL+E group.
The authors concluded that exercise training plus a weight loss program improves DLPA, sleep efficiency and depressionand asthma symptoms in obese adults with asthma.
The three-month program targeted both weight loss and exercise through aerobic and resistance training, the study authors wrote in the journal Medicine and Science in Sports and Exercise.
When contacted over the email Dr Celso R F Carvalho gave the following insights into the study "In my opinion, the more important results of our study are the fact that exercise reduced the comorbidities of the obese asthmatic patients. I am not aware of any other non-pharmacological intervention that has presented such strong impact (bariatric surgery or diet support).

This is important because, in our clinical practice, most patients complain about having problems sleeping, lack of energy (sedentarism) and lower self-esteem (maybe due to the depression symptoms).

It is also important to reinforce that the effect in our study is compared with patients having an important support (nutritional and psychological). Then, the exercise had, on average, a 3-fold effect size compared with the "control group".

At last, I consider that the association we evaluated (Figures 4A-D) also suggest (or explain) how improvement in daily steps and depression symptoms are explained."

Read the findings of the study here.