Functional impact of sequelae in drug-susceptible and multidrug-resistant tuberculosis

BACKGROUND: Evidence on the impact of tuberculosis (TB) treatment on lung function is scarce. The aim of this study was to evaluate post-treatment sequelae in drug-susceptible and drug-resistant-TB (DR-TB) cases in Mexico and Italy.METHODS: At the end of TB treatment the patients underwent complete clinical assessment, functional evaluation of respiratory mechanics, gas exchange and a 6-minute walking test. Treatment regimens (and definitions) recommended by the World Health Organization were used throughout.RESULTS: Of 61 patients, 65.6% had functional impairment, with obstruction in 24/61 patients (39.4%), and 78% with no bronchodilator response. These effects were more prevalent among DR-TB cases (forced expiratory volume in 1 s/forced vital capacity [FEV1/FVC] < lower limit of normality, 14/24 vs. 10/34; P = 0.075). DR-TB patients showed moderately severe (FEV1 < 60%) and severe obstruction (FEV1 < 50%) (P = 0.008). Pre- and post-bronchodilator FEV1 and FEV1/FVC (% of predicted) were significantly lower among DR-TB cases. Plethysmography abnormalities (restriction, hyperinflation and/or air trapping) were more frequent among DR-TB cases (P = 0.001), along with abnormal carbon monoxide diffusing capacity (DLCO) (P = 0.003).CONCLUSION: The majority of TB patients suffer the consequences of post-treatment sequelae (of differing levels), which compromise quality of life, exercise tolerance and long-term prognosis. It is therefore important that lung function is comprehensively evaluated post-treatment to identify patient needs for future medication and pulmonary rehabilitation.

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Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.18.0779 ◽

2019 ◽

Vol 23 (10) ◽

pp. 1050-1054

Author(s):

L. Guglielmetti ◽

J. Jaffré ◽

C. Bernard ◽

F. Brossier ◽

N. El Helali ◽

...

Keyword(s):

Multidrug Resistant ◽

New Drugs ◽

World Health ◽

Advisory Committees ◽

Treatment Regimens ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Health Organization

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

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Assessing the impacts of short-course multidrug-resistant tuberculosis treatment in the Southeast Asia Region using a mathematical modeling approach

PLoS ONE ◽

10.1371/journal.pone.0248846 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248846

Author(s):

Win Min Han ◽

Wiriya Mahikul ◽

Thomas Pouplin ◽

Saranath Lawpoolsri ◽

Lisa J. White ◽

...

Keyword(s):

Southeast Asia ◽

Treatment Initiation ◽

Multidrug Resistant ◽

Treatment Regimens ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Short Course ◽

Mdr Tb ◽

The Impact

This study aimed to predict the impacts of shorter duration treatment regimens for multidrug-resistant tuberculosis (MDR-TB) on both MDR-TB percentage among new cases and overall MDR-TB cases in the WHO Southeast Asia Region. A deterministic compartmental model was constructed to describe both the transmission of TB and the MDR-TB situation in the Southeast Asia region. The population-level impacts of short-course treatment regimens were compared with the impacts of conventional regimens. Multi-way analysis was used to evaluate the impact by varying programmatic factors (eligibility for short-course MDR-TB treatment, treatment initiation, and drug susceptibility test (DST) coverage). The model predicted that overall TB incidence will be reduced from 246 (95% credible intervals (CrI), 221–275) per 100,000 population in 2020 to 239 (95% CrI, 215–267) per 100,000 population in 2035, with a modest reduction of 2.8% (95% CrI, 2.7%–2.9%). Despite the slight reduction in overall TB infections, the model predicted that the MDR-TB percentage among newly notified TB infections will remain steady, with 2.4% (95% CrI, 2.1–2.9) in 2020 and 2.5% (95% CrI, 2.3–3.1) in 2035, using conventional MDR-TB treatment. With the introduction of short-course regimens to treat MDR-TB, the development of resistance can be slowed by 38.6% (95% confidence intervals (CI), 35.9–41.3) reduction in MDR-TB case number, and 37.6% (95% CI, 34.9–40.3) reduction in MDR-TB percentage among new TB infections over the 30-year period compared with the baseline using the standard treatment regimen. The multi-way analysis showed eligibility for short-course treatment and treatment initiation greatly influenced the impacts of short-course treatment regimens on reductions in MDR-TB cases and percentage resistance among new infections. Policies which promote the expansion of short-course regimens and early MDR-TB treatment initiation should be considered along with other interventions to tackle antimicrobial resistance in the region.

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Impact of Lung Biopsy on Lung Function in Idiopathic Pulmonary Fibrosis

Respiration ◽

10.1159/000509557 ◽

2020 ◽

pp. 1-8

Author(s):

Pierre-Henri Aussedat ◽

Nader Chebib ◽

Kais Ahmad ◽

Jean-Charles Glerant ◽

Gabrielle Drevet ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Forced Vital Capacity ◽

Lung Biopsy ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Surgical Lung Biopsy ◽

Before And After ◽

The Impact

Background: Video-assisted surgical lung biopsy (SLB) is performed in 10–30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF). Objectives: The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF. Methods: This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB. Results: In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline. Conclusion: In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year.

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Tuberculosis: Development of New Drugs and Treatment Regimens

Jurnal Respirasi ◽

10.20473/jr.v7-i.1.2021.36-45 ◽

2021 ◽

Vol 7 (1) ◽

pp. 36

Author(s):

Soedarsono Soedarsono

Keyword(s):

Treatment Guidelines ◽

New Drugs ◽

World Health ◽

Health Crisis ◽

Treatment Regimens ◽

Tb Treatment ◽

Repurposed Drugs ◽

Latent Tb Infection ◽

Health Organization ◽

Who Guideline

Tuberculosis (TB) still becomes a public health crisis. Drug-resistant TB (DR-TB) becomes a concern as the increasing DR-TB cases in countries with high TB burden. The 2017 World Health Organization (WHO) guideline recommended a combination of TB treatment consisting of 2 months of intensive phase with isoniazid (H), rifampisin (R), pyrazinamid (Z), and ethambutol (E), followed by 4 months of continuation phase with HR daily. WHO has updated DR-TB treatment guidelines several times. In 2016, WHO recommended shorter regimen and individual regimen based on certain conditions. The most updated 2020 WHO guideline recommended the short regimen consisting of all oral drugs as well as changes in the grouping of medicines used in DR-TB regimens in longer/individual regimens. Bedaquiline, delamanid, pretomanid, and sutezolid are new drugs which have been studied for their uses as anti-TB drugs (ATD). Bedaquilin and delamanid, which have passed phase 3 trials, have been approved and recommended by WHO for DR-TB treatment. Repurposed drugs have been used for DR-TB treatment during the time of evaluation of drugs list and regimens for DR-TB treatment. Fluoroquinolones, clofazimine, linezolid, carbapenem, amoxicillin/clavulanic acid are repurposed drugs. TB and DR-TB management will be updated at any time, based on the latest findings in studies, to evaluate and improve the effectiveness of current treatments. Prevention of active TB disease by the treatment of latent TB infection (LTBI) is also a critical component of the end TB strategy by WHO. Therefore, the development of new drugs for the LTBI treatment is also needed.

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The impact of body mass index, central obesity and physical activity on lung function: results of the EpiHealth study

ERJ Open Research ◽

10.1183/23120541.00214-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00214-2020

Author(s):

Magnus Svartengren ◽

Gui-Hong Cai ◽

Andrei Malinovschi ◽

Jenny Theorell-Haglöw ◽

Christer Janson ◽

...

Keyword(s):

Physical Activity ◽

Body Mass Index ◽

Lung Function ◽

Body Mass ◽

Physical Inactivity ◽

Central Obesity ◽

Forced Expiratory Volume ◽

Normal Weight ◽

Weight Group ◽

The Impact

Study objectivesObesity is often associated with lower lung function; however, the interaction of lung function with central obesity and physical inactivity is less clear. As such, we investigated the effect on lung function of body size (body mass index (BMI)), central obesity (waist circumference (WC)) and self-reported physical activity.MethodsLung function, height, weight and WC were measured in 22 743 participants (12 791 women), aged 45–75 years, from the EpiHealth cohort study. Physical activity, gender and educational level were assessed using a questionnaire.ResultsObesity, central obesity and physical inactivity were all associated with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). However, in participants without central obesity there was an increase in both FEV1 and FVC by BMI (% predicted FVC increasing from median 98%, interquartile range (IQR) 89–110% in underweight participants (BMI <20) to 103%, IQR 94–113% in obese participants (BMI ≥30)). In contrast, there was a decrease in % predicted FVC in participants with central obesity (from 98%, IQR 89–109% in the normal weight group to 95%, IQR 85–105% in the obese weight group). We further found a negative association between physical activity and lung function among those with low and high levels of physical activity (% predicted FEV1 97%, IQR 86–107% versus 103%, IQR 94–113%, respectively and % predicted FVC 96%, IQR 85–106% versus 103%, IQR 94–113%, respectively). All results remained when calculated by z-scores.ConclusionsThe association between BMI and lung function is dependent on the presence of central obesity. Independent of obesity, there is an association between physical activity and lung function.

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Ambient air pollution exposure and lung function assessment of filling station attendants in Ibadan, Nigeria

Reviews on Environmental Health ◽

10.1515/reveh-2018-0027 ◽

2019 ◽

Vol 34 (2) ◽

pp. 211-218

Author(s):

Toluwanimi Mobolade Oni ◽

Godson R.E.E. Ana

Keyword(s):

Air Pollution ◽

Lung Function ◽

Air Pollutants ◽

Ambient Air ◽

Forced Expiratory Volume ◽

Ambient Air Pollution ◽

World Health ◽

Health Administration ◽

Cross Sectional ◽

Filling Station

Abstract Background There is an increasing range of adverse health effects associated with air pollution at very low concentrations. Few studies have assessed respiratory parameters among filling station attendants. Objectives This study assessed air pollutants; particulate matter (PM10) and total volatile organic compounds (TVOC) concentrations at filling stations as well as determined forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR) levels among filling station attendants. Methods A cross-sectional study was conducted to assess PM10 and TVOC concentrations at 20 systematically selected filling stations in Ibadan North Local Government Area, Ibadan for 2 months using a Thermo Scientific pDR 1500 PM10 monitor and SF2000-TVOC meter. FEV1 and PEFR levels were measured in order to assess the effect of exposure to PM10 and TVOC on lung function of 100 filling station attendants using a PIKO-1 Electronic peakflow/FEV1 meter. Results Total mean PM10 concentrations (μg/m3) in the morning (43.7±16.5) and afternoon (27.8±7.9) were significantly lower (p<0.01) than the World Health Organization (WHO) guideline limit (50 μg/m3). Total mean TVOC concentrations (ppm) in the morning (12.0±3.4) and afternoon (5.6±2.4) were however significantly higher (p<0.01) than the Occupational Safety and Health Administration (OSHA) guideline limit (3 ppm). Mean FEV1 for filling station attendants was 1.63±0.39 and PEFR was 171.7±45.9. Conclusion Filling stations are hotspots for the emission of VOCs and PM10. However, filling station attendants in this study are at risk of exposure to high concentrations of VOCs but not PM10. FEV1 and PEFR values among filling station attendants were very low which could possibly be attributed to extended exposure to air pollutants. Regular medical examinations should also be conducted on filling station attendants in order to aid early detection of deviations in their health status.

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The impact of PM2.5 on lung function in adults with asthma

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0394 ◽

2020 ◽

Vol 24 (6) ◽

pp. 570-576

Author(s):

L. Qibin ◽

L. Yacan ◽

J. Minli ◽

Z. Meixi ◽

L. Chengye ◽

...

Keyword(s):

Lung Function ◽

Meta Analysis ◽

Forced Expiratory Volume ◽

Risk Of Bias ◽

Biomedical Literature ◽

Knowledge Infrastructure ◽

Acute Asthma Exacerbation ◽

Pm2.5 Exposure ◽

The Impact ◽

Chinese National Knowledge Infrastructure

OBJECTIVE: To conduct a systematic review of the literature and assess the effect of PM2.5 (particulate matter with diameter <2.5 μm) exposure on lung function in adults with asthma.METHODS: We searched all literature published between 1 January 2010 and 26 March 2019 in the EMBASE, PubMed, Cochrane Central Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) databases. The studies were assessed for analytic methods, risk of bias and results of statistical analysis.RESULTS: The selected studies all had a low or moderate risk of bias. Overall, PM2.5 exposure was positively associated with a decrease in forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC) in adults with asthma (standardised mean difference 0.20, 95% CI 0.02–0.38; P = 0.03).CONCLUSION: We observed a negative correlation between PM2.5 exposure and FEV1/FVC in patients with asthma. Our meta-analysis provides evidence suggesting that PM2.5 is a risk factor for acute asthma exacerbation in adults.

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The Bewildering Antitubercular Action of Pyrazinamide

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.00070-19 ◽

2020 ◽

Vol 84 (2) ◽

Cited By ~ 4

Author(s):

Elise A. Lamont ◽

Nicholas A. Dillon ◽

Anthony D. Baughn

Keyword(s):

Mode Of Action ◽

Rational Design ◽

Multidrug Resistant ◽

Future Research ◽

Therapeutic Approaches ◽

Treatment Regimens ◽

Tb Treatment ◽

Short Course ◽

Recent Developments ◽

Susceptibility And Resistance

SUMMARY Pyrazinamide (PZA) is a cornerstone antimicrobial drug used exclusively for the treatment of tuberculosis (TB). Due to its ability to shorten drug therapy by 3 months and reduce disease relapse rates, PZA is considered an irreplaceable component of standard first-line short-course therapy for drug-susceptible TB and second-line treatment regimens for multidrug-resistant TB. Despite over 60 years of research on PZA and its crucial role in current and future TB treatment regimens, the mode of action of this unique drug remains unclear. Defining the mode of action for PZA will open new avenues for rational design of novel therapeutic approaches for the treatment of TB. In this review, we discuss the four prevailing models for PZA action, recent developments in modulation of PZA susceptibility and resistance, and outlooks for future research and drug development.

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Understanding how geographic, demographic and treatment history impact health outcomes of patients with multi-drug-resistant tuberculosis in Pakistan, 2014–2017

Epidemiology and Infection ◽

10.1017/s0950268820002307 ◽

2020 ◽

Vol 148 ◽

Author(s):

F. Iqbal ◽

M. K. Defer ◽

A. Latif ◽

H. Hadi

Keyword(s):

Large Family ◽

Multidrug Resistant ◽

Incidence Rates ◽

Diagnostic Methods ◽

Diagnosis And Treatment ◽

World Health ◽

Sociocultural Factors ◽

Second Line ◽

Tb Treatment ◽

Mdr Tb

Tuberculosis (TB) is one of the top 10 leading causes of morbidity and mortality worldwide [1]. In 2017, approximately 10 million people were infected with TB and 1.3 million patients faced mortality [1]. Patients with active TB can infect up to 10–15 people over a year. There is a greater risk of transmission in overcrowded areas with limited air ventilation including large family units, prisons and slums [1, 2]. Without proper diagnosis and treatment, roughly 45% of non-HIV positive TB patients face mortality [1]. With the help of global organizations and national TB treatment and control programmes, the global incidence of TB is declining by approximately 2% each year [1]. The World Health Organization (WHO) TB-strategy aims to end the TB epidemic and encourages partners to fund national TB programmes to improve diagnosis and treatment of TB. The goal is to ultimately decrease death rates by 90% and decrease incidence rates by 80% [1]. To achieve these goals, the decline in TB incidence needs to reach approximately 4–5% per year [1]. The WHO 2018 TB report identified multidrug resistant TB (MDR-TB) as the leading factor hindering that goal [1]. The incidence and spread of MDR-TB has drastically increased, where approximately 558 000 new cases of MDR-TB were diagnosed in 2017 causing more than 230 000 deaths globally [1]. MDR-TB is identified by resistance to the two most powerful anti-TB treatment drugs including isoniazid and rifampicin [3]. Patients with MDR-TB are required to start second-line anti-TB drugs (SLDs), which are limited, expensive, less effective and more toxic [1,2]. Therapy duration is one of the major limitations of second-line treatments, which may require up to two years of consistent use. Since TB affects mostly developing countries, long treatment durations and associated costs become a major challenge. In 2015, 15% of new TB cases were reported as MDR-TB, which drastically increased to 24% by 2017 [1]. Even with significant improvements in molecular tests and diagnostic methods, MDR-TB is still on the rise where the success rate of treatments is between 50 and 60% [1]. Additional characteristics including socioeconomic and sociocultural factors need to be considered when targeting and treating patients with MDR-TB.

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Lung function over the life course of paediatric and adult patients with cystic fibrosis from a large multi-centre registry

Scientific Reports ◽

10.1038/s41598-020-74502-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Arul Earnest ◽

Farhad Salimi ◽

Claire E. Wainwright ◽

Scott C. Bell ◽

Rasa Ruseckaite ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Mixed Model ◽

Linear Mixed Model ◽

Pancreatic Insufficiency ◽

Forced Expiratory Volume ◽

Rate Of Change ◽

Data Registry ◽

Mortality Outcome ◽

The Impact

Abstract A key measure of lung function in people with Cystic Fibrosis (CF) is Forced Expiratory Volume in the first second FEV1 percent predicted (FEV1pp). This study aimed to address challenges in identifying predictors of FEV1pp, specifically dealing with non-linearity and the censoring effect of death. Data was obtained from a large multi-centre Australian Cystic Fibrosis Data Registry (ACFDR). A linear mixed model was used to study FEV1pp as the endpoint. There were 3655 patients (52.4% male) included in our study. Restricted cubic splines were used to fit the non-linear relationship between age of visit and FEV1pp. The following predictors were found to be significant in the multivariate model: age of patient at visit, BMI z-score, age interaction with lung transplantation, insulin dependent diabetes, cirrhosis/portal hypertension, pancreatic insufficiency, Pseudomonas aeruginosa infection and baseline variability in FEV1pp. Those with P. aeruginosa infection had a lower mean difference in FEV1pp of 4.7 units, p < 0.001 compared to those who did not have the infection. Joint modelling with mortality outcome did not materially affect our findings. These models will prove useful for to study the impact of CFTR modulator therapies on rate of change of lung function among patients with CF.

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