Classifying new anti-tuberculosis drugs: Rationale and future perspectives

The classification of anti-tuberculosis (TB) drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO) has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2-5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification) and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed

controlling the disease

Surveillance and outbreak reports Surveillance of extensively drug-resistant tuberculosis in Europe, 2003-2007 15 by I Devaux, D Manissero, K Fernandez de la Hoz, K Kremer, D van Soolingen, on behalf of the EuroTB network Analysis of tuberculosis treatment outcomes in the European Union and European Economic Area: efforts needed towards optimal case management and control 21 by D Manissero, V Hollo, E Huitric, C Ködmön, A Amato-Gauci Risk of developing tuberculosis from a school contact: retrospective cohort study

Effectiveness of a Pulmonary Rehabilitation Program on Persistent Asthma Stratified for Severity

BACKGROUND: Asthma is defined by airway inflammation associated with various respiratory symptoms, and pharmacologic treatment is based on inhaled corticosteroids and bronchodilators. Physical activity, educational training, nutritional support, and psychological counseling are considered part of non-pharmacologic treatment; however, studies so far have investigated the effect of single non-pharmacologic treatment. There are few studies that demonstrate the effect of comprehensive pulmonary rehabilitation, but no clear data are available regarding factors that can predict who could benefit the most. Our study aimed to assess the effect of a comprehensive 3-week pulmonary rehabilitation program on exercise tolerance and to identify baseline subject characteristics that may predict a better response to treatment. METHODS: This was a retrospective study. A team planned a pulmonary rehabilitation program: educational support; endurance training; and optional components, such as respiratory exercises and airway clearance techniques. The following data were collected before and after pulmonary rehabilitation: subject characteristics, smoking history, asthma severity, respiratory function and 6-min walk test (6MWT). RESULTS: We collected data on 515 subjects (202 males 39.2%), age, mean \ub1 SD 63.9 \ub1 10.4 y), with 413 (80.2%) having moderate-to-severe disease; and 455 (88.4%) with stable respiratory symptoms 455 (88.35%). At baseline, the percentage of predicted 6MWT in all subjects categorized by the Global Initiative for Asthma (GINA) steps was in the normal range, except for the subjects at step 5, for which it was significantly lower (P = .01). All subjects showed a significant improvement in exercise tolerance and oxygen saturation, together with a decrease in baseline dyspnea, muscle fatigue, and heart rate after pulmonary rehabilitation. Improvement of 6MWT was statistically significant, irrespective of the GINA categorization. The variables related to the improvement in 6MWT were age (P < .001), smoking habit (P = .034), and baseline 6MWT (P < .001). CONCLUSIONS: Subjects with asthma at any GINA step seemed to benefit from a pulmonary rehabilitation program; analysis of our data highlighted that pulmonary rehabilitation was more beneficial in younger subjects with a smoking history and worse baseline exercise tolerance

Effect of pulmonary rehabilitation on heart rate recovery in adult individuals with asthma or chronic obstructive pulmonary disease

Introduction: Heart rate recovery (HRR) after exercise is a marker of disease severity and prognosis in cardiovascular and respiratory disorders. More than 30% of adult individuals with asthma may show a slow HRR. Pulmonary rehabilitation improves exercise capacity in individuals with asthma or chronic obstructive pulmonary disease (COPD). Aim: The study aimed to evaluate the effect of pulmonary rehabilitation on HRR in individuals with asthma as compared to those with COPD. Methods: Retrospective analysis of HRR one minute after the six-minute walking test (6MWT) was performed before and after an exercise training program. The COPD Assessment Test (CAT), Barthel Index-Dyspnea (BI-D), Medical Research Council (MRC) score for dyspnea, and the Five-Times-Sit-to-Stand test (5STS) were also assessed as secondary outcome measures. Results: Slow HRR prevalence was significantly lower in individuals with asthma than with COPD (29.1 vs. 46.7%, respectively: p = 0.003). Post-program HRR did not change in more than 70% of individuals in either population and improved in 16% of both populations, whereas it actually worsened in 12 and 10% of individuals with asthma and COPD, respectively. The outcome measures significantly improved in both populations, irrespective of baseline HRR. Conclusion: In individuals with asthma or COPD, exercise training does not significantly improve HRR

Thyroid hormones modifications among COVID-19 patients undergoing pulmonary rehabilitation

Introduction: Patients with severe COVID-19 often experience long-lasting disabilities that can improve after pulmonary rehabilitation. Moreover patients with severe COVID-19 display thyroid function alterations due to a non-thyroidal illness syndrome (NTIS). The aim of our study was to evaluate thyroid function parameters among patients hospitalized for COVID-19 who were eligible or not to respiratory rehabilitation and their modifications during follow-up. Materials and methods: Post-COVID-19 patients referred to a Respiratory Rehabilitation Unit were evaluated. Outpatients, not candidate for rehabilitation, were enrolled as Control group. Patients who had completed a 4-week-rehabilitation program were enrolled as Rehabilitation Group. All patients were evaluated at T0 (4 weeks after the discharge home in Control Group and after completion of rehabilitation in Rehabilitation Group) and at T1 (3 months after T0). Results: The final study group included 39 patients (20 in the Rehabilitation group and 19 in the Control group). Patients in the Rehabilitation Group had more frequently received invasive or non-invasive ventilation, had a longer length-of-stay in referring hospitals, had a higher number of comorbidities and displayed a worse performance at 6-minute-walking-test (6MWT) and Short-Physical-Performance-Battery-test (SPPB). FT3 values were lower at T0 in the Rehabilitation Group, while TSH and FT4 values were similar in the two groups. While no significant modifications in thyroid-function-parameters were observed in the Control Group, a significant increase in FT3 value was observed in the Rehabilitation Group at T1. Participants of both groups had improved the results of 6MWT at T1, while SPPB values improved only in the Rehabilitation Group. Conclusions: COVID-19 patients after pulmonary rehabilitation experience an increase in FT3 values during follow-up, paralleled with an amelioration of functional capabilities

The respiratory rehabilitation Maugeri network service reconfiguration after 1 year of COVID-19

As part of the Italian Health Service the respiratory ICS Maugeri network were reconfigured and several in-hospital programs were suspended to be substituted by workforce and facilities reorganization for acute and post-acute COVID-19 care need. The present review shows the time course variation of respiratory ICS network in terms of admissions diagnosis and outcomes. A comparative review of the admissions and outcome measures data (anthropometric, admission diagnosis, provenience, comorbidities, disability, symptoms, effort tolerance, disease impact, length of stay and discharge destinations) over 1 year period (March 2020-March 2021) was undertaken and compared to retrospective data from a corresponding 1 year (March 2019-March 2020) period to determine the impact of the network relocation on the delivery of pulmonary specialist rehabilitation to patients with complex needs during the pandemic episode. One of the changes implemented at the respiratory Maugeri network was the relocation of the Pulmonary Rehabilitation units from its 351 beds base to a repurposed 247 beds and a reduction in total number of admitted patients (n=3912 in pre-COVID time; n=2089 in post-COVID time). All respiratory diagnosis, except COVID sequelae, decreased (chronic respiratory failure-CRF, COPD, obstructive sleep apnoea syndrome-OSAS, interstitial lung disease-ILD, tracheostomized patients and other mixed diseases decreased of 734, 705, 157, 87, 79 and 326 units, respectively). During the pandemic time, 265 post COVID sequelae with CRF were admitted for rehabilitation (12.62%), percentage of patients coming from acute hospital increased, LOS and NIV use remained stable while CPAP indication decreased. Disease impact, dyspnoea and effort tolerance as their improvements after rehabilitation, were similar in the two periods. Only baseline disability, expressed by Barthel index, seems higher in the 2 observation time as its improvement. Hospital deaths and transfers to acute hospitals were higher during pandemic crisis while home destination decreased. This review demonstrated impact of coronavirus pandemic situation, specifically the relocation of the respiratory inpatient rehabilitation wards in a huge Italian network

Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up

Background: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. Methods: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. Results: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83–0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. Conclusions: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils

The effect of benralizumab on inflammation in severe asthma: a real-life analysis

Background: Benralizumab is a monoclonal antibody treatment for severe eosinophilic asthma (SEA). Few studies investigated its role in airway inflammation and its correlation with lung function. Objectives: The aim of the present study is to assess its effect after 1 year of treatment, focusing on airway inflammation. Design: This is a retrospective observational study, in an Italian tertiary reference centre specialised in diagnosis and management of severe asthma patients. Methods: We conducted a monocentric retrospective study including SEA patients treated with benralizumab for 1 year. Clinical, functional and inflammatory data were collected at baseline, 6 (T6) and 12 (T12) months. Results: Twenty-two SEA patients on benralizumab were included. We observed a reduction in exacerbations rate and systemic steroid treatment (p < 0.0001) as well as an improvement in asthma control (p < 0.0001), health-related quality of life (p = 0.017) and lung function pre-BD FEV1 (L) (p = 0.02) and percentage (p = 0.004) and post-BD FEV1 (L) (p = 0.01) and percentage (p = 0.003) from baseline to T6 and T12. A reduction in sputum eosinophil percentage was observed at T6 and T12 (p < 0.005). We found a positive correlation between the variation of sputum eosinophils percentage and FEV1 (L) at T12 (rho = −0.79, p = 0.04). Moreover, the improvement of FEF25%–75% from baseline to 6 (rho = −0.53, p = 0.03) and 12 (rho = −0.62, p = 0.01) months negatively correlated with the duration of asthma disease. In our cohort 12/22 patients were super-responders at T6 and 15/22 at T12. Furthermore, clinical remission was reached by 12/22, and all of them obtained blood and sputum eosinophils counts normalisation. Conclusion: Our data confirm that it is a rapid and effective treatment for SEA acting on clinical, functional, systemic and airway inflammatory outcomes. Our results highlight the role of induced sputum as a promising non-invasive technique to investigate pathophysiologic mechanisms in severe asthma treated with biologics. Finally, a negative correlation between small airway improvement and the duration of asthma may suggest that a prompt referral to asthma centres may delay lung function worsening. Additional studies are needed to investigate more in-depth the role of induced sputum in the management of asthma, response to treatment and remission

Time course of exercise capacity in patients recovering from covid-19-associated pneumonia

Objective: High prevalences of muscle weakness and impaired physical performance in hospitalized patients recovering from COVID-19-associated pneumonia have been reported. Our objective was to determine whether the level of exercise capacity after discharge would affect long-term functional outcomes in these patients. Methods: From three to five weeks after discharge from acute care hospitals (T0), patients underwent a six-minute walk test (6MWT) and were divided into two groups according to the distance walked in percentage of predicted values: <75% group and ≥75% group. At T0 and three months later (T1), patients completed the Short Physical Performance Battery and the Euro Quality of Life Visual Analogue Scale, and pulmonary function and respiratory muscle function were assessed. In addition, a repeat 6MWT was also performed at T1. Results: At T0, 6MWD values and Short Physical Performance Battery scores were lower in the <75% group than in the ≥75% group. No differences were found in the Euro Quality of Life Visual Analogue Scale scores, pulmonary function variables, respiratory muscle function variables, length of hospital stay, or previous treatment. At T1, both groups improved their exercise capacity, but only the subjects in the <75% group showed significant improvements in dyspnea and lower extremity function. Exercise capacity and functional status values returned to predicted values in all of the patients in both groups. Conclusions: Four weeks after discharge, COVID-19 survivors with exercise limitation showed no significant differences in physiological or clinical characteristics or in perceived health status when compared with patients without exercise limitation. Three months later, those patients recovered their exercise capacity

Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases

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