Shashi Bellam

What evidence implicates airway smooth muscle in the cause of BHR

Bronchial hyperresponsiveness (BHR), the occurrence of excessive bronchoconstriction in response to relatively small constrictor stimuli, is a cardinal feature of asthma. Here, we consider the role that airway smooth muscle might play in the generation of BHR. The weight of evidence suggests that smooth muscle isolated from asthmatic tissues exhibits normal sensitivity to constrictor agonists when studied during isometric contraction, but the increased muscle mass within asthmatic airways might generate more total force than the lesser amount of muscle found in normal bronchi. Another salient difference between asthmatic and normal individuals lies in the effect of deep inhalation (DI) on bronchoconstriction. DI often substantially reverses induced bronchoconstriction in normals, while it often has much less effect on spontaneous or induced bronchoconstriction in asthmatics. It has been proposed that abnormal dynamic aspects of airway smooth muscle contraction—velocity of contraction or plasticity-elasticity balance—might underlie the abnormal DI response in asthma. We suggest a speculative model in which abnormally long actin filaments might account for abnormally increased elasticity of contracted airway smooth muscle.

Fatal spontaneous rectus sheath hematoma in a patient with cirrhosis

Rectus sheath hematoma (RSH) is an uncommon and often misdiagnosed condition. This well-described entity is typically self-limited. In rare cases, the condition may be fatal. We report a case of a patient with cirrhosis who died of progressive RSH and its subsequent complications.

Nuclear Import of Serum Response Factor in Airway Smooth Muscle

We have previously shown that the transcription-promoting activity of serum response factor (SRF) is partially regulated by its extranuclear redistribution. In this study, we examined the cellular mechanisms that facilitate SRF nuclear entry in canine tracheal smooth muscle cells. We used in vitro pull-down assays to determine which karyopherin proteins bound SRF and found that SRF binds KPNA1 and KPNB1 through its nuclear localization sequence. Immunoprecipitation studies also demonstrated direct SRF-KPNA1 interaction in HEK293 cells. Import assays demonstrated that KPNA1 and KPNB1 together were sufficient to mediate rapid nuclear import of SRF-GFP. Our studies also suggest that SRF is able to gain nuclear entry through an auxiliary, nuclear localization sequence-independent mechanism.

African-American race and mortality in interstitial lung disease: a multicentre propensity-matched analysis

We studied whether African-American race is associated with younger age and decreased survival time at diagnosis of interstitial lung disease (ILD). We performed a multicentre, propensity score-matched analysis of patients with an ILD diagnosis followed at five US hospitals between 2006 and 2016. African-Americans were matched with patients of other races based on a time-dependent propensity score calculated from multiple patient, physiological, diagnostic and hospital characteristics. Multivariable logistic regression models were used. All-cause mortality and hospitalisations were compared between race-stratified patient cohorts with ILD, and sensitivity analyses were performed. The study included 1640 patients with ILD, 13% of whom were African-American, followed over 5041 person-years. When compared with patients of other races, African-Americans with ILD were younger at diagnosis (56 years versus 67 years), but in the propensity-matched analyses had greater survival (hazard ratio 0.46, 95% CI 0.28–0.77; p=0.003) despite similar risk of respiratory hospitalisations (relative risk 1.04, 95% CI 0.83–1.31; p=0.709), and similar GAP-ILD (gender–age–physiology-ILD) scores at study entry. Sensitivity analyses in a separate cohort of 9503 patients with code-based ILD diagnosis demonstrated a similar association of baseline demographic characteristics with all-cause mortality. We conclude that African-Americans demonstrate a unique phenotype associated with younger age at ILD diagnosis and perhaps longer survival time. African-American ILD subjects are younger, less often male and may have greater survival than other racial groups http://ow.ly/mvFQ30jOJAi

Predicting Pulmonary Function from Phone Sensors

Abstract Introduction: Smartphones are ubiquitous, but it is unknown what physiological functions can be monitored at clinical quality. Pulmonary function is a standard measure of health status for cardiopulmonary patients. We have shown phone sensors can accurately measure walking patterns. Here we show that improved classification models can accurately predict pulmonary function, with sole inputs being motion sensors from carried phones. Subjects and Methods: Twenty-five cardiopulmonary patients performed 6-minute walk tests in pulmonary rehabilitation at a regional hospital. They carried smartphones running custom software recording phone motion. Each patients pulmonary function was measured by spirometry. A universal model, based on support vector machine, then computed the category of function with input from signal processing features and patient demographic features. Results: All but a few of every 10-second interval for every patient was correctly predicted. The trained model perfectly computed the GOLD (Global Initiative for Chronic Obstructive Lung Disease) level 1/2/3, which is a standard classification of pulmonary function. Each level was determined to have a characteristic motion, which could be recognized from the sensor features. In addition, longitudinal changes were detected for 10 patients with multiple walk tests, except for cases with clinical instability. Conclusions: These results are encouraging toward clinical validation of passive monitors running continuously in the background, for patients in homes during daily activities. Initial testing indicates the same high accuracy as with active monitors, for patients in hospitals during walk tests. We expect patients can simply carry their phones during everyday living, while models support automatic prediction of pulmonary function for health monitoring.

Improving Asthma Outcomes in the Digital Era: A Systematic Review

BackgroundLack of adherence remains a major cause of poor asthma outcomes. Technology-based interventions to promote adherence to asthma controller medications are emerging.ObjectiveThis systematic review aimed to evaluate digital interventions to improve adherence to asthma controller medications and clinical outcomes.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this review identified studies using medication electronic monitoring devices (EMDs), mobile applications including smartphone applications (SPAs) or MP3 players, web-based portals, and multimodal interventions to improve asthma outcomes.ResultsOf the 25 interventions identified, 23 resulted in a positive outcome within the limits of the study. Two of the three EMDs, zero of the five mobile applications, zero of the 11 web portals, and three of the seven multimodal interventions showed objectively measured improvement in controller medication adherence.ConclusionsStudies featuring EMD technology alone or as part of a multimodal intervention demonstrate promise in improving controller medication adherence. SPA technology both alone and in combination with other digital interventions demonstrates improvements in asthma control and quality of life. Future studies are needed to isolate the most efficacious component(s) of these interventions.