Comparison of a Novel Regimen of Rifapentine, Tedizolid, and Minocycline with Standard Regimens for Treatment of Pulmonary Mycobacterium kansasii.

The combination of isoniazid, rifampin, and ethambutol is recommended by the American Thoracic Society (ATS) for treatment of pulmonary Mycobacterium kansasii, while the British Thoracic Society (BTS) recommends clarithromycin, rifampin and ethambutol. Unfortunately, therapy duration for both regimens lasts for years. In this study, we administered tedizolid, minocycline, clarithromycin, and rifapentine as monotherapy as well as novel combinations in the intracellular hollow-fiber model system of M. kansasii (HFS-Mkn) in a 28-day study. The ATS and BTS regimens were used as comparators. Repetitive sampling was used to validate the intended intrapulmonary pharmacokinetics of each drug and to monitor changes in M. kansasii burden. As monotherapy, tedizolid at an observed area under the concentration-time curve from 0 to 24 h (AUC0-24)/MIC of 5.85 and minocycline at an AUC0-24/MIC of 5.77 failed to kill the bacteria below day 0 (stasis), clarithromycin at an AUC0-24/MIC of 2.4 held the bacterial burden at stasis, but rifapentine at an AUC0-24/MIC of 140 killed 2 log10 CFU/ml below stasis. The BTS regimen kill slope was -0.083 ± 0.035 CFU/ml/day, which was significantly superior to the ATS regimen slope of -0.038 ± 0.038 CFU/ml/day. The rifapentine-tedizolid-minocycline combination kill slope was -0.119 ± 0.031 CFU/ml/day, superior to that of the ATS regimen and comparable to that of the BTS regimen. In conclusion, the BTS regimen and the novel rifapentine-tedizolid-minocycline regimen showed better kill of intracellular bacteria in the HFS-Mkn However, the efficacy of the new combination regimen remains to be tested in clinical settings.

Validation of respiratory questionnaire for lung function assessment among an occupational group of textile workers in Pakistan.

OBJECTIVE: To determine the association of spirometric lung pattern with respiratory symptoms and to validate the American Thoracic Society respiratory questionnaire for lung function assessment among textile workers. METHODS: This cross-sectional survey was conducted from August to December 2009 among adult textile workers of Karachi. Data was collected through the American Thoracic Society Division of Lung Disease respiratory questionnaire and the lung function was assessed by using a spirometer. Results of three acceptable readings of spirogram were recorded and the best of the three readings was used for analysis. SPSS 19 was used for data analysis. RESULTS: There were 372 participants in the study with an overall mean age of 27±8.5 years. In linear regression analysis, forced expiratory volume in one second for workers who had chronic cough was -829.1 (confidence interval: -1273.1, -385.2), chronic wheeze -168.8 (confidence interval: -319.3, -18.2) and shortness of breath grade 2 -215.6 (confidence interval: -387.8, -43.4). In logistic regression model, after adjusting for covariates, odds of reduced percentage predicted forced expiratory volume in one second for workers who had chronic cough was 3.09 (confidence interval: 1.26, 7.56), chronic wheeze 1.98 (confidence interval: 1.05, 3.71) and shortness of breath grade 2 2.07 (confidence interval: 1.05, 4.07), while odds of reduced percentage predicted forced vital capacity for shortness of breath grade 2 was 2.35 (confidence interval: 1.05, 5.21). In logistic regression model 2, for assessing the effect of different combinations of chronic respiratory symptoms, the odds of reduced percentage predicted forced expiratory volume in one second for the combination of cough and wheeze was 2.08 (confidence interval: 1.05, 4.10), cough and shortness of breath grade 2 2.47 (confidence interval: 1.18, 5.18), phlegm and shortness of breath grade 2 2.59 (confidence interval: 1.23, 5.43), cough, wheeze and shortness of breath grade 2 4.64 (confidence interval: 1.97, 10.93)and cough, phlegm, wheeze and shortness of breath grade 2 4.18 (confidence interval: 1.68, 10.37). CONCLUSIONS: A combination of chronic respiratory symptoms was best associated with decrements in lung function.

Pulmonary outcome in former preterm, very low birth weight children with bronchopulmonary dysplasia: a case-control follow-up at school age.

OBJECTIVE: To assess and compare long-term pulmonary outcomes in former preterm-born, very low birth weight (VLBW) children with and without bronchopulmonary dysplasia (BPD) born in the surfactant era. STUDY DESIGN: Pulmonary function tests (ie, spirometry, body plethysmography, and gas transfer testing) were performed in children with a history of VLBW and BPD (n = 28) and compared with a matched preterm-born VLBW control group (n = 28). Medical history was evaluated by questionnaire. RESULTS: At time of follow-up (mean age, 9.5 years), respiratory symptoms (36% vs 8%) and receipt of asthma medication (21% vs 0%) were significantly more frequent in the preterm-born children with previous BPD than in those with no history of BPD. The children with a history of BPD had significantly lower values for forced expiratory volume in 1 second (z-score -1.27 vs -0.4; P = .008), forced vital capacity (z-score -1.39 vs -0.71 z-score; P = .022), and forced expiratory flow rate at 50% of forced vital capacity (z-score -2.21 vs -1.04; P = .048) compared with the preterm control group. CONCLUSION: Preterm-born children with a history of BPD are significantly more likely to have lung function abnormalities, such as airway obstruction and respiratory symptoms, at school age compared with preterm-born children without BPD.

Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects.

BACKGROUND: Fraction of exhaled nitric oxide (Feno) and blood eosinophil count (B-Eos) values, markers of local and systemic eosinophilic inflammation, respectively, are increased in asthmatic patients. Little is known about the relation of these markers to reported wheeze and asthma events in a random population sample. OBJECTIVES: We sought to determine the individual and independent values of B-Eos and Feno in relation to wheeze, asthma diagnosis, and asthma events in a cross-sectional study. METHODS: Feno and B-Eos values were measured in 12,408 subjects aged 6 to 80 years from the National Health and Nutrition Examination Survey 2007-2008 and 2009-2010. Current wheeze and asthma diagnosis, as well as asthma attacks and asthma-related emergency department (ED) visits within the last 12 months, were assessed by means of questionnaires. RESULTS: Intermediate or high Feno values and intermediate or high B-Eos values were independently associated with having asthma, wheeze, and asthma attacks. However, only intermediate and high B-Eos values were independently associated with asthma-related ED visits. High Feno (≥ 50 ppb) and B-Eos (≥ 500 cells/mm(3)) values rendered an adjusted odds ratio of 4.5 of having wheeze, 5.1 of having asthma, 5.4 for asthma attacks, and 2.9 for asthma-related ED visits compared with normal Feno (<25 ppb) and B-Eos (<300 cells/mm(3)) values. CONCLUSIONS: Exhaled nitric oxide and B-Eos values offered independent information in relation to the prevalence of wheeze, asthma diagnosis, and asthma events in this random population sample. The clinical importance of these findings in asthmatic patients with regard to phenotyping and individualized treatment, considering both local and systemic eosinophilic inflammation, needs to be determined.

Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients.

BACKGROUND: Recent meta-analyses of genome-wide association studies in general populations of European descent have identified 28 loci for lung function. OBJECTIVE: We sought to identify novel lung function loci specifically for asthma and to confirm lung function loci identified in general populations. METHODS: Genome-wide association studies of lung function (percent predicted FEV1 [ppFEV1], percent predicted forced vital capacity, and FEV1/forced vital capacity ratio) were performed in 4 white populations of European descent (n = 1544), followed by meta-analyses. RESULTS: Seven of 28 previously identified lung function loci (HHIP, FAM13A, THSD4, GSTCD, NOTCH4-AGER, RARB, and ZNF323) identified in general populations were confirmed at single nucleotide polymorphism (SNP) levels (P < .05). Four of 32 loci (IL12A, IL12RB1, STAT4, and IRF2) associated with ppFEV1 (P < 10(-4)) belong to the TH1 or IL-12 cytokine family pathway. By using a linear additive model, these 4 TH1 pathway SNPs cumulatively explained 2.9% to 7.8% of the variance in ppFEV1 values in 4 populations (P = 3 × 10(-11)). Genetic scores of these 4 SNPs were associated with ppFEV1 values (P = 2 × 10(-7)) and the American Thoracic Society severe asthma classification (P = .005) in the Severe Asthma Research Program population. TH2 pathway genes (IL13, TSLP, IL33, and IL1RL1) conferring asthma susceptibility were not associated with lung function. CONCLUSION: Genes involved in airway structure/remodeling are associated with lung function in both general populations and asthmatic subjects. TH1 pathway genes involved in anti-virus/bacterial infection and inflammation modify lung function in asthmatic subjects. Genes associated with lung function that might affect asthma severity are distinct from those genes associated with asthma susceptibility.

Assessing Respiratory Tract Infections' Prevalence and Microbial Profiles in Mechanically Ventilated Patients: Insights From Broncho Alveolar Lavage Examination.

Introduction Chest infections represent a significant challenge in mechanically ventilated patients, often leading to adverse outcomes despite advancements in critical care. This prospective study was conducted in the intensive care unit of tertiary referral care, with objectives to assess chest infection prevalence, microbial profiles, and outcomes in mechanically ventilated patients through broncho-alveolar lavage (BAL) examination. Methodology This prospective study involved 38 patients aged 15 to 65 years who were receiving mechanical ventilation and underwent BAL. The procedure of BAL was followed as per the guidelines and recommendations outlined by the American Thoracic Society for Bronchoscopic Lavage. Microbial analysis involves the use of microscopic examination and quantitative culture methods. Different staining techniques were utilized to identify bacteria, fungi, and mycobacteria. Complications and adverse events were monitored and recorded. Results Out of the 38 patients who underwent BAL, the majority, 30 (78.94%), were found to have chest infections, with gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, being the causative agents. The antibiotic sensitivity profiles indicated that the organisms were susceptible to carbapenems and broad-spectrum ß-lactam/ß-lactamase inhibitor combinations while showing resistance to fluoroquinolones. Despite adequate treatment, mortality remained significant in 12 (31.57%) patients. Conclusion Study findings underscore the importance of proactive surveillance, early diagnosis, and targeted management strategies to mitigate the burden of respiratory infections in critical care settings.

Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis.

PRM-151, recombinant human Pentraxin-2 (PTX-2) also referred to as serum amyloid P (SAP), is under development for treatment of fibrosis. A First-in-Human (FIH) trial was performed to assess the safety, tolerability, and pharmacokinetics of single ascending intravenous doses of PRM-151 administered to healthy subjects, using a randomized, blinded, placebo controlled study design. Each cohort included three healthy subjects (PRM-151:placebo; 2:1). SAP levels were assessed using a validated ELISA method, non-discriminating between endogenous and exogenous SAP. At a dose level of 10 mg/kg, at which a physiologic plasma level of SAP was reached, two additional healthy volunteers and three pulmonary fibrosis (PF) patients were enrolled enabling comparison of the pharmacokinetic SAP profile between healthy volunteers and PF patients. In addition, the percentage of fibrocytes (CD45+/Procollagen-1+ cells) in whole blood samples was assessed to demonstrate biological activity of PRM-151 in the target population. PRM-151 administration was generally well tolerated. In two pulmonary fibrosis patients non-specific, transient skin reactions (urticaria and erythema) were observed. PRM-151 administration resulted in a 6-to 13-fold increase in mean baseline plasma SAP levels at dose levels of 5, 10, and 20 mg/kg. The estimated t1/2 of PRM-151 in healthy volunteers was 30 h. Pharmacokinetic profiles were comparable between healthy volunteers and PF patients. PRM-151 administration resulted in a 30-50% decrease in fibrocyte numbers 24 h post-dose. This suggests that administration of PRM-151 may be associated with a reduction of fibrocytes in PF patients, a population for which current pharmacotherapeutic options are limited. The pharmacological action of PRM-151 should be confirmed in future research.

A combined inspiratory and expiratory muscle training program improves respiratory muscle strength and fatigue in multiple sclerosis.

OBJECTIVE: To determine the effects of a short-duration, combined (inspiratory and expiratory), progressive resistance respiratory muscle training (RMT) protocol on respiratory muscle strength, fatigue, health-related quality of life, and functional performance in individuals with mild-to-moderate multiple sclerosis (MS). DESIGN: Quasi-experimental before-after trial. SETTING: University rehabilitation research laboratory. PARTICIPANTS: Volunteers with MS (N=21) were divided into 2 groups: RMT (n=11; 9 women, 2 men; mean age ± SD, 50.9 ± 5.7y, mean Expanded Disability Status Scale score ± SD, 3.2 ± 1.9) and a control group that did not train (n=10; 7 women, 3 men; mean age ± SD, 56.2 ± 8.8y, mean Expanded Disability Status Scale score ± SD, 4.4 ± 2.1). Expanded Disability Status Scale scores ranged from 1 to ≤6.5. No patients withdrew from the study. INTERVENTION: Training was a 5-week combined progressive resistance RMT program, 3d/wk, 30 minutes per session. MAIN OUTCOME MEASURES: The primary outcome measures were maximal inspiratory pressure and expiratory pressure and the Modified Fatigue Impact Scale. All subjects completed secondary measures of pulmonary function, the six-minute walk test, the timed stair climb, the Multiple Sclerosis Self-Efficacy Scale, the Medical Outcomes Study 36-Item Short-Form Health Survey, and the Physical Activity Disability Scale. RESULTS: Maximal inspiratory pressure and expiratory pressure (mean ± SD) increased 35% ± 22% (P<.001) and 26% ± 17% (P<.001), respectively, whereas no changes were noted in the control group (12% ± 23% and -4% ± 17%, respectively). RMT improved fatigue (Modified Fatigue Impact Scale, P<.029), with no change or worsening in the control group. No changes were noted in the six-minute walk test, stair climb, Multiple Sclerosis Self-Efficacy Scale, or Physical Activity Disability Scale in the RMT group. The control group had decreases in emotional well-being and general health (Medical Outcomes Study 36-Item Short-Form Health Survey). CONCLUSIONS: A short-duration, combined RMT program improved inspiratory and expiratory muscle strength and reduced fatigue in patients with mild to moderate MS.

A Retrospective Analysis of Vitamin D Levels in Hospitalized COVID-19 Patients With Suspected Pulmonary Embolism.

Introduction Despite using anti-coagulation therapy in hospitalized coronavirus disease 2019 (COVID-19) patients, they have high rates of pulmonary embolism (PE) and deep vein thrombosis (DVT). The main objective of this study was to evaluate the association between vitamin D deficiency and thrombotic events (defined as the occurrence of a new PE or DVT) in hospitalized COVID-19 patients. Materials and Methods This was a retrospective, cross-sectional study of 208 hospitalized COVID-19 patients who received a computed tomographic pulmonary angiography (CTPA) based on clinical suspicion of PE between January 1, 2020, and February 5, 2021. A <20 ng/mL serum vitamin D level was used to categorize vitamin D deficiency. Nonparametric tests and multivariate binary logistic regression were used to evaluate the association between serum vitamin D levels and clinical outcomes. Results The mean vitamin D level was 26.7±13.0 ng/mL (n=208), and approximately one-third of patients were vitamin D deficient (n=68, 32.7%). No association was found between vitamin D deficiency and the occurrence of thrombotic events. The incidence of PE was 19.1% in vitamin D deficient patients compared to 11.4% in vitamin D sufficient patients (p=0.13). Vitamin D deficiency was positively associated with ICU admission (OR 3.047, 95%CI 1.57-5.91, p=0.001) and mortality (OR 3.76, 95%CI 1.29-11.01, p=0.016). Conclusions This study found no association between vitamin D deficiency and the occurrence of a new PE or DVT in hospitalized COVID-19 patients. Patients with vitamin D deficiency were more likely to be admitted to the ICU and had increased overall mortality.

Bronchodilator Responsiveness Defined by the 2005 and 2021 ERS/ATS Criteria in Patients with Asthma as Well as Chronic Obstructive Pulmonary Disease.

Background: In the 2021 ERS/ATS interpretive strategies for routine lung function tests, a positive bronchodilator response (BDR) was updated as a change of >10% relative to the predicted value in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC). We aimed to explore the differences between the 2005 and 2021 ERS/ATS criteria applied to patients with asthma as well as chronic obstructive pulmonary disease (COPD). Methods: BDR test data about asthma patients aged 6-80 years and COPD patients aged 18-80 years were derived from the National Respiratory Medicine Center, First Affiliated Hospital of Guangzhou Medical University, from January 2017 to March 2022. BDR results defined by the 2005 and 2021 ERS/ATS criteria were named 2005-BDR and 2021-BDR, respectively. We compared differences between 2005-BDR and 2021-BDR and analyzed the trend in the proportion of positive BDR (BDR+) with the level of airflow obstruction. Results: A total of 4457 patients with asthma and 7764 patients with COPD were included in the analysis. The percentages of 2005-BDR+ and 2021-BDR+ were 63.32% and 52.84% for asthma, 30.92% and 22.94% for COPD, respectively. Of patients with 2005-BDR+, 81.86% for asthma and 70.18% for COPD showed 2021-BDR+ results, and these patients had higher FEV1%pred, FVC%pred (all P<0.05). Whichever BDR criterion was adopted, the proportion of BDR+ had an upward linear trend with the increased degree of airflow obstruction in COPD, but exhibited an approximate inverted U-shaped curve in asthma. In COPD, the proportion of BDRFEV1 was negatively associated with the degree of airflow obstruction, while BDRFVC was positively associated (all P<0.05). Conclusion: Compared with 2005-BDR+, the proportion of 2021-BDR+ reduced markedly in patients with asthma and COPD, but their trends with the degree of airflow obstruction did not change. Patients with consistent BDR+ had higher initial FEV1%pred and FVC%pred.

Hepatic sarcoidosis: Clinical characteristics and outcome.

BACKGROUND & AIMS: Clinical manifestation of hepatic involvement in sarcoidosis can vary from asymptomatic disease to severe complications such as cirrhosis and portal hypertension. However, data on hepatic sarcoidosis are limited, and evidence-based recommendations are lacking. Our study aimed to assess the features and clinical course of hepatic sarcoidosis in a predominantly Caucasian cohort. METHODS: We performed a retrospective study including all patients with hepatic sarcoidosis between 2004 and 2020 in 5 German centres. The median follow-up time was 36 months (range 0.0-195). Data on demographic parameters, clinical manifestations, diagnostic test results, treatment, and outcome were collected. RESULTS: A total of 1,476 patients with sarcoidosis and 62 patients with hepatic involvement (4.2%) were identified. Of the patients, 51.6% were female, and 80.6% were Caucasian. Most patients were asymptomatic and were observed to have a cholestatic pattern of liver enzyme elevations. Cirrhosis was detected in 9 patients (14.5%), of whom 6 developed clinical manifestations of portal hypertension. Fifty-four patients were medically treated, most commonly with glucocorticoids (69.4%) or ursodeoxycholic acid (UDCA) (40.3%). Levels of alkaline phosphatase (ALP) decreased by 60.8% on average from baseline in patients treated with glucocorticoids and by 59.9% in patients treated with UDCA. Seventeen patients received treatment augmentation with a second line agent, of whom 8 patients normalised ALP levels during follow-up. None of the patients underwent liver transplantation or developed hepatocellular carcinoma (HCC). Three of the patients died during follow-up owing to liver-related complications. CONCLUSIONS: Hepatic involvement in sarcoidosis was found in 4.2% of patients with sarcoidosis and was clinically significant in 14.5% of those. These findings highlight the importance of early identifying, monitoring, and treating hepatic sarcoidosis, given its increased mortality when associated with end-stage liver disease. LAY SUMMARY: Clinical diagnostic and surveillance of hepatic involvement in sarcoidosis has not been standardised, and management of hepatic involvement is a clinical challenge, since it remains poorly characterised in many ways. Our results show that one-third of patients with hepatic sarcoidosis presented with clinically significant portal hypertension, 14.5% suffered from cirrhosis, and 3 patients died owing to liver-related complications. Regarding pharmacological treatment options, corticosteroids and UDCA were the medical agents most frequently used, and both of them have been shown to induce biochemical response in the majority of patients. These findings highlight the importance of correctly and early identifying hepatic involvement in sarcoidosis, because of the potentially progressive course of disease.

Complexity of design in early phase respiratory clinical trials; evaluating impact of primary endpoints and sponsor size.

Asthma and COPD represent most of the clinical trials in the respiratory area. The Primary Endpoint (PE) defines how trials are conducted. We hypothesised that small and mid-sized pharmaceutical companies may be innovative in the selection of their trial endpoints, to be time- and cost-effective. To test this, a record of industry-sponsored phase II trials in asthma, COPD and Asthma/COPD over 11 years was obtained. The type of PE and the influence these had on length, number of subjects and investigational trial sites were evaluated for the different disease categories. Differences in the type of PE used by large versus small/mid-sized companies were found for both asthma and COPD trials (p = 0.011 and 0.025), with sponsorship influencing the conduction of these. In asthma, studies sponsored by large companies were significantly longer than those from smaller companies (p = 0.0001). Additionally, large companies intended to recruit more subjects (asthma: p = 0.0048, COPD: p ≤ 0.0001) and use more investigational sites (asthma: p = 1 × 10-7, COPD: p = 1 × 10-5) than those from small and mid-size companies. A sub-analysis of the time and subject requirements associated with each type of PE did not provide an explanation for the differences observed. In conclusion, this exploratory analysis indicates differences in study size, duration and type of PE used by small/mid-sized and large companies. For some types of endpoints, differences in length and study size were found. However, it wasn't possible to attribute these differences between sponsors solely to the choice of PE, pointing out to the complexity of running clinical trials.

Interstitial lung abnormality (ILA) and nonspecific interstitial pneumonia (NSIP).

This review article aims to address mysteries existing between Interstitial Lung Abnormality (ILA) and Nonspecific Interstitial Pneumonia (NSIP). The concept and definition of ILA are based upon CT scans from multiple large-scale cohort studies, whereas the concept and definition of NSIP originally derived from pathology with evolution to multi-disciplinary diagnosis. NSIP is the diagnosis as Interstitial Lung Disease (ILD) with clinical significance, whereas only a part of subjects with ILA have clinically significant ILD. Eventually, both ILA and NSIP must be understood in the context of chronic fibrosing ILD and progressive ILD, which remains to be further investigated.

Approach to the diagnosis and treatment of non-tuberculous mycobacterial disease.

Non-tuberculous mycobacteria (NTM) is a collective name given to a group of more than 190 species of Mycobacterium. The clinical presentation for most NTM infections is non-specific, often resulting in delayed diagnosis. Further complicating matters is that NTM organisms can be difficult to isolate. Medications used to treat NTM infection can be difficult for patients to tolerate, and prolonged courses of anti-mycobacterial therapy are often required for adequate suppression or eradication. Herein, we review different NTM syndromes, appropriate diagnostic tests, and treatment regimens.

Interobserver variability in high-resolution CT of the lungs.

PURPOSE: To quantify the interobserver variability among the most frequently encountered parenchymal patterns in High Resolution CT (HRCT) and to compare the interobserver variability in the application of the 2011 and 2018 usual interstitial pneumonia (UIP) criteria according to the joint guidelines from international thoracic and respiratory societies. MATERIAL AND METHODS: Two observers independently evaluated 126 HRCT, with examples of most common parenchymal patterns, and noted the presence of each pattern. The readers also noted whether the findings met the 2011 criteria for UIP. In a second reading, the same readers noted whether the HRCT met the UIP criteria according to the 2018 UIP update. RESULTS: The kappa values for interobserver variability for the different patterns ranged from 0.28 (intralobular lines) to 0.85 (tree-in-bud nodules). The kappa value for UIP pattern was similar for 2011 and 2018 criteria, 0.58 and 0.69, respectively. Compared to the 2011 UIP criteria, there was no statistically significant difference in the number of HRCT classified as UIP using the 2018 criteria. CONCLUSIONS: There is a substantial variation in interobserver agreement between the different parenchymal patterns, which suggests that some patterns a more easily identified than others. There is also a considerable reader variation in the assessment of UIP applying the 2011 UIP criteria as well as applying the 2018 UIP update.

Costs incurred by patients with drug-susceptible pulmonary tuberculosis in semi-urban and rural settings of Western India.

BACKGROUND: India reports the highest number of tuberculosis (TB) cases worldwide. Poverty has a dual impact as it increases the risk of TB and exposes the poor to economic hardship when they develop TB. Our objective was to estimate the costs incurred by patients with drug-susceptible TB in Bhavnagar (western India) using an adapted World Health Organization costing tool. METHODS: We conducted a descriptive cross-sectional study of adults, notified in the public sector and being treated for drug-susceptible pulmonary TB during January-June 2019, in six urban and three rural blocks of Bhavnagar region, Gujarat state, India. The direct and indirect TB-related costs, as well as patients' coping strategies, were assessed for the overall care of TB till treatment completion. Catastrophic costs were defined as total costs > 20% of annual household income (excluding any amount received from cash transfer programs or borrowed). Median and interquartile range (IQR) was used to summarize patient costs. The median costs between any two groups were compared using the median test. The association between any two categorical variables was tested by the Pearson chi-squared test. All costs were described in US dollars (USD). During the study period, on average, one USD equalled 70 Indian Rupees. RESULTS: Of 458 patients included, 70% were male, 62% had no formal education, 71% lived in urban areas, and 96% completed TB treatment. The median (IQR) total costs were USD 8 (5-28), direct medical costs were USD 0 (0-0), direct non-medical costs were USD 3 (2-4) and indirect costs were USD 6 (3-13). Among direct non-medical costs, travel cost (median = USD 3, IQR: 2-4) to attend health facilities were the most prominent, whereas the indirect costs were mainly contributed by the patient's loss of wages (median = USD 3, IQR: 0-6). Four percent of patients faced catastrophic costs, 11% borrowed money to cover costs and 7% lost their employment; the median working days lost to TB was 30 (IQR: 15-45). A majority (88%) of patients received a median USD 43 (IQR: 41-43) as part of a cash transfer program for TB patients. CONCLUSIONS: Treatment completion was high and the costs incurred by TB patients were low in this setting. However, negative financial consequences occur even in low-cost settings. The role of universal cash transfer programs in such settings requires further study.

A novel pathophysiologic link between upper and lower airways in patients with chronic rhinosinusitis: Association of sputum periostin levels with upper airway inflammation and olfactory function.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma are collectively called unified airway diseases. Periostin has been implicated in the pathophysiologic link of these conditions but only by serum measurements. We sought to investigate sputum levels of periostin and their association with upper airway inflammation and olfactory function in CRS patients. METHODS: We prospectively recruited 56 CRS patients who underwent endoscopic sinus surgery (20 with and 36 without comorbid asthma), and 28 healthy controls between October 2015 and December 2017. Lower and upper airway indices such as sputum periostin levels and eosinophil and neutrophil counts, exhaled fractional nitric oxide (FeNO) levels, and olfactory function were evaluated in the three groups. Radiological severity of CT images and tissue eosinophilia of surgical specimens were also assessed in the CRS patients. RESULTS: Sputum periostin levels were highest, and olfactory function was most impaired, in the CRS patients with comorbid asthma, followed by those without asthma and controls in this order. CRS with asthma group showed higher sputum eosinophils and FeNO levels than the other two groups, while CRS patients without asthma showed significantly higher neutrophils in sputum than the other two groups. When confined to CRS patients, olfactory dysfunction was correlated with sputum eosinophil counts. Eosinophil counts of nasal polyps showed a significant positive correlation with sputum periostin and FeNO levels. Radiological severity of CRS was correlated with sputum eosinophil counts and FeNO levels. CONCLUSIONS: Periostin levels and inflammatory cells such as eosinophils and neutrophils in the lower airways are increased in patients with CRS, suggesting the presence of mutual interactions between upper and lower airways even if asthma does not coexist. Olfactory dysfunction and eosinophilic nasal polyps may be potential indicators of Th2-driven inflammation in the lower airways. TRIAL REGISTRATION: This study was registered on the UMIN Clinical Trials Registry (Registry ID UMIN000018672).

FEV1 decline in relation to blood eosinophils and neutrophils in a population-based asthma cohort.

BACKGROUND: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies. OBJECTIVE: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort. METHODS: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline. RESULTS: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses. CONCLUSIONS AND CLINICAL RELEVANCE: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.

A case series and literature review of multiple sclerosis and COVID-19: Clinical characteristics, outcomes and a brief review of immunotherapies.

BACKGROUND: In view of the emerging coronavirus pandemic, the demand for knowledge about the impact of SARS-CoV-2 on people with Multiple Sclerosis (MS) continues to grow. Patients receiving disease modifying therapy (DMT) for MS have a higher background risk of infection-related health care utilization when compared to the general population. Therefore, there is a need of evidence-based recommendations to reduce the risk of infection and also managing MS patients with SARS-CoV-2. CASE DESCRIPTION: We present three patients with history of Multiple Sclerosis (MS) on DMTs presenting with worsening MS symptoms likely pseudo exacerbation who were diagnosed with COVID-19. DISCUSSION: An extensive review of 7 articles was performed, in addition to a brief review on DMTs use in MS patients with COVID-19. In our cases, all patients were on DMT and severe course of disease was noted in 2 cases. No fatality was observed. CONCLUSIONS: This review provides a base on the clinical characteristics, outcomes and the roles of DMTs in MS patients suffering from n-cov-2. Physicians need to be vigilant about considering COVID-19 infection related relapse in the MS patients, especially in this COVID-19 pandemic era and look for pseudo-exacerbation. As most cases are found to have mild course and full recovery on DMTs, further research is needed to formulate evidence-based guidelines. This review will particularly be helpful for the researchers and registries to collect future data on MS and COVID-19.

Evaluating the real-life effect of MP-AzeFlu on asthma outcomes in patients with allergic rhinitis and asthma in UK primary care.

BACKGROUND: MP-AzeFlu (Dymista®; spray of azelastine/fluticasone propionate) is the most effective allergic rhinitis (AR) treatment available. Its effect on asthma outcomes in patients with AR and asthma is unknown. METHODS: This pre-post historical cohort study, using the Optimum Patient Care Research Database, included patients aged ≥12 years, from UK general practice with active asthma (defined as a recorded diagnosis, with ≥1 prescription for reliever or controller inhaler) in the year before or at the initiation date. The primary study outcome was change in number of acute respiratory events (i.e. exacerbation or antibiotic course for a respiratory event) between baseline and outcome years. The effect size of MP-AzeFlu was quantified as the difference in % of patients that improved and worsened. RESULTS: Of the 1,188 patients with AR and asthma included, many had a record of irreversible obstruction (67%), and uncontrolled asthma (70.4%), despite high mean daily doses of reliever/controller therapy and acute oral corticosteroid use, in the year pre-MP-AzeFlu initiation. MP-AzeFlu initiation was associated with fewer acute respiratory events (effect size (e) = 5.8%, p = 0.0129) and a reduction in daily use of short-acting ß2-agonists, with fewer patients requiring >2 SABA puffs/week (e = 7.7% p < 0.0001). More patients had well-controlled asthma 1-year post-MP-AzeFlu initiation (e = 4.1%; p = 0.0037), despite a reduction in inhaled corticosteroids (e = 4.8%; p = 0.0078). CONCLUSIONS: This study provides the first direct evidence of the beneficial effect of MP-AzeFlu on asthma outcomes in co-morbid patients in primary care in the United Kingdom. TRIAL REGISTRATION: EUPAS30940. Registered August 13, 2019.