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.

Evaluation of physical activity before and after respiratory rehabilitation in normal weight individuals with asthma: a feasibility study.

Background: Individuals with asthma spend less time engaging in physical activity compared to the general population. Increasing physical activity has become a patient-centered goal for the treatment of treatable traits of individuals with asthma. There are data showing the possible effects of a pulmonary rehabilitation program on physical activity in obese individuals with asthma but not in normal-weight asthmatics. The objective of this feasibility study is to estimate the number of daily steps and time spent on activity in normal-weight individuals with asthma, measured before and after a pulmonary rehabilitation program. Methods: Normal-weight individuals with moderate to severe asthma were evaluated. The individuals measured their daily steps with an accelerometer for 5 days before and after a pulmonary rehabilitation program. The study was registered on ClinicalTrials.gov: NCT05486689. Results: In total, 17 participants were enrolled; one dropout and data on the time in activity of two individuals are missing due to a software error during the download. Data from 16 patients were analyzed. The median number of steps/day at baseline was 5,578 (25th, 75th percentiles = 4,874, 9,685) while the median activity time was 214 min (25th, 75th percentiles = 165, 239). After the rehabilitation program, the number of daily steps increased by a median value of 472 (p-value = 0.561) and the time in activity reduced by 17 min (p-value = 0.357). We also found a significant difference in quality of life, muscle strength, and exercise capacity. Conclusions: The results of this study make it possible to calculate the sample size of future studies whose main outcome is daily steps in normal-weight individuals with asthma. The difficulties encountered in downloading time in activity data do not allow the same for this outcome. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05486689.

Unlocking the Long-Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three-Year Real-Life Study.

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV1) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety.

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease.

Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

Pulmonary rehabilitation and risk of fall in elderly with chronic obstructive pulmonary disease.

BACKGROUND: Few data are available on the effects of pulmonary rehabilitation (PR) on risk of fall in over 80 individuals with chronic obstructive pulmonary disease (COPD). We investigated the effectiveness of PR on the risk of fall in older as compared to younger than 80 individuals. METHODS: Parallel-group retrospective exploratory study of individuals undergone in-hospital PR. The risk of fall was defined as a gait speed ≤0.8 m/s (primary outcome). Outcome measures (exercise capacity, physical performance, symptoms, and health status) were also assessed. RESULTS: As compared to younger, individuals over 80 suffered from more severe symptoms, a reduction in physical performance and in exercise capacity and greater risk of fall (P=0.0001). The proportion of participants at risk of fall increased with age, and after PR decreased significantly without any significant difference between age groups. However, 53.4% of older individuals were still at risk of fall, as compared to 17.5% of those under 80 (P=0.0001). After PR, both populations had improved outcomes measures, without any significant between group differences. CONCLUSIONS: In individuals with COPD pulmonary rehabilitation reduced the risk of fall, while improving outcome measures independent of age, however, more than 50% of those over 80 were still at risk of fall. The pulmonary rehabilitation programs for individuals over 80 should include strategies effective in reducing the risk of fall.

Brittle Asthma: Still on Board?

(1) Background: "Brittle Asthma" was considered an asthma clinical phenotype and deemed to be life-threatening in the early 2000s; then, this definition disappeared. The purpose of this review is to examine what has historically been referred to as this term and see whether it may be applied to modern clinical practice, thus acquiring fresh relevance and meaning. (2) Methods: A non-systematic search of the literature was conducted using both MeSH and free-text phrases. No limitations on the research design or type of publication were applied. (3) Results: Reliable data regarding "Brittle Asthma" are lacking due to the paucity of current data and the few studies available. After a few years of reworking, it was divided into two sub-classes: one characterized by a wide PEF variability despite high-dose therapy and the other by sudden acute attacks in otherwise apparently normal airway functions or well-controlled asthma. Their characteristics were hardly defined because of their low prevalence. Data regarding risk factors, atopy, mechanisms, and treatments were analyzed. (4) Conclusions: Over time, different terminology has been introduced to define asthma severity and control. It would be worth investigating whether the term "Brittle Asthma" previously used may be helpful to find new hints to stratify patients and improve disease management.

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.

Determinants of response to hypercapnia and to progressive and transient hypoxia in obstructive sleep apnea patients.

BACKGROUND: The knowledge regarding the control of breathing during wakefulness in patients affected by obstructive sleep apnea (OSAS) is still challenging. The aim of this study is firstly to analyze hypoxic and hypercapnic ventilatory response in OSA patients in comparison to controls and secondly, to investigate correlations between chemosensivity and both lung function tests, such as arterial blood gas analysis and spirometric parameters, and clinical characteristics, such as age and BMI. METHODS: Seventeen never treated OSA patients (16M; 53±13.2 years; BMI=34.5±8.1; AHI=45±14.7) underwent nocturnal cardiopulmonary monitoring test, complete lung function tests (spirometry, lung volumes and arterial blood gas analysis on room air). Read's rebreathing test was used to evaluate hypercapnic ventilatory response (HVRCO2); hypoxic ventilatory response (HVRO2) was studied through progressive and transient methods. The response was expressed in terms of slope of linear regression for HVRCO2 and of hyperbolic curve for HVRO2 between minute ventilation (VE) or mean inspiratory flow (VT/Ti) and PetCO2 or PetO2. RESULTS: The OSA group showed increased transient, but not progressive, HVRO2 and a lower HVRCO2. A lower HVRCO2 was predicted by greater values of BMI (P<0.01). Progressive HVRO2 increased with age and lower FEV1/VC, while transient HVRO2 (P<0.05) was inversely correlated with the nocturnal lowest SaO2 (P<0.01). CONCLUSIONS: Nocturnal intermittent hypoxic stimuli increases daytime glomic reactivity to transient hypoxia, while BMI is the main independent determinants of the bulbar response to hypercapnia in normocapnic OSAS patients.

An overview of Cochrane systematic reviews for pulmonary rehabilitation interventions in people with chronic obstructive pulmonary disease: a mapping synthesis.

INTRODUCTION: There is a global unmet need for rehabilitation to meet which the World Health Organization, in collaboration with Cochrane Rehabilitation, is developing the Package of Interventions for Rehabilitation with the aim of identifying rehabilitation interventions relevant to a range of key health conditions, including chronic obstructive pulmonary disease (COPD). The purpose of this paper is to describe the best available evidence on pulmonary rehabilitation interventions for people with COPD. EVIDENCE ACQUISITION: An Overview of Cochrane Systematic Reviews (CSRs). Through the search strategy, COPD-related systematic reviews published from January 2009 to November 2021 were identified. Data were extracted on each reported outcome related to an intervention and judgements about the quality of evidence were made, using the GRADE approach. EVIDENCE SYNTHESIS: Seventeen reviews were analyzed, for a total of 314 primary studies that included 22,206 participants. CSRs provided information on the effectiveness of rehabilitation on functioning, activity, quality of life, anxiety, depression, mortality, and health care resource utilization. CONCLUSIONS: Our findings report that comprehensive pulmonary rehabilitation programs and water exercises improve the exercise capacity and quality of life (QoL) in people with COPD. Different exercise modalities, intensities, and settings for different muscle groups, breathing exercises, and counseling can improve exercise capacity, QoL, dyspnea, hospitalizations, and physical activity. It is uncertain whether breathing exercise, low-intensity exercise, neuromuscular electrical stimulation, and psychological intervention have an effect on exercise capacity, dyspnea, QoL, and physical activity. The protocol was registered on OSF (registration DOI: 10.17605/OSF.IO/8A26Q).

Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease / Recomendações da Sociedade Brasileira de Pneumologia e Tisiologia para o manejo da doença pulmonar pós-tuberculose

ABSTRACT Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

RESUMO Historicamente, todos os esforços contra a tuberculose concentraram-se no diagnóstico rápido e no tratamento efetivo para quebrar a cadeia de transmissão do Mycobacterium tuberculosis. No entanto, nos últimos anos, têm sido encontradas mais e mais evidências sobre as dramáticas consequências da condição definida como doença pulmonar pós-tuberculose (DPPT). Aproximadamente um terço dos pacientes que sobrevivem à tuberculose pulmonar enfrenta morbidades consideráveis e persistentes, incluindo comprometimento respiratório, desafios psicossociais e redução da qualidade de vida relacionada à saúde após o término do tratamento. Diante da importante carga global e local da tuberculose, bem como da carga estimada da DPPT, considerou-se urgente o desenvolvimento de um documento de consenso por uma sociedade científica brasileira - a Sociedade Brasileira de Pneumologia e Tisiologia (SBPT) - para a prevenção e manejo dessa condição, a fim de alocar recursos de forma adequada para e nos serviços de tuberculose e servir de guia para os profissionais de saúde. Uma equipe de onze pneumologistas e um metodologista foi criada pela SBPT para revisar as evidências atuais sobre a DPPT e desenvolver recomendações adaptadas ao contexto brasileiro. O painel de especialistas selecionou os temas com base nas evidências atuais e diretrizes internacionais. Durante a primeira fase, três membros do painel redigiram as recomendações, que foram divididas em três seções: definição e prevalência de DPPT, avaliação da DPPT e manejo da DPPT. Na segunda fase, todos os membros do painel analisaram, discutiram e revisaram as recomendações até chegar a um consenso. O documento foi aprovado formalmente pela SBPT em sessão especial organizada durante o Congresso Anual da SBPT de 2023.

Analysis of Patients with Asthma and Mixed Granulocytic Inflammatory Pattern in Sputum.

BACKGROUND: Patients with asthma usually present airway inflammation classified as eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic pattern according to sputum inflammatory cells. OBJECTIVE: The aim of the study was to analyze clinical and biological characteristics of patients with asthma and mixed granulocytic pattern in comparison with the other groups. METHODS: Induced sputum was used to assess airway inflammation; lung function was evaluated as well as blood leukocytes and disease control. History of comorbidities was collected. RESULTS: We retrospectively analyzed 231 subjects with asthma; patients with mixed granulocytic pattern were more frequently male compared with paucigranulocytic subjects, older than eosinophilic and paucigranulocytic patients with increased number and vitality of sputum cells compared to eosinophilic and paucigranulocytic patients and higher cumulative illness rating score, related to increased age. Smoking history, age of disease onset, and ICS treatment were not associated with higher mixed granulocytic pattern occurrence. Subjects with neutrophilic inflammation (mixed granulocytic and neutrophilic patterns considered altogether) were more frequently obese. In subjects under 67 years of age (median of the enrolled subjects), arterial hypertension was the only comorbidity more frequent in mixed granulocytic than in the other groups. 137/231 subjects were re-valuated during follow-up. Lung function of patients with mixed granulocytic, neutrophilic, and paucigranulocytic patterns improved less than that of eosinophilic patients. CONCLUSION: Aging and presence of comorbidities, in particular obesity and hypertension, are characteristics of patients with asthma and mixed granulocytic pattern. They could respond less well to treatment than eosinophilic patients.

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.

Patients and doctors group meetings: an innovative way to explore severe asthma backstage.

Severe asthma patients' life is heavily influenced by the disease, which has impact on personal and professional choices or general lifestyle. Despite the available tools to help physicians investigating the patient-reported outcomes there is a need for a more standardised and structured approach to include the evaluation of quality of life together with the emotions of patients into the routine clinical interaction. We hereby report the use of an active listening and insight approach to understand the emotions of patients with severe asthma through dedicated in-person meetings involving a group of patients with their doctors, caregivers and an external moderator. The initiative "Patients insight meeting" was organized within 17 specialist referral centres for severe asthma in Italy in 2019 and involved 149 patients. Insights related to 4 different items were collected and a task force composed by the external moderators produced a general report including the suggestions from the participating centres. This experience of group-meetings involving both patients and doctors together represents an innovative way to investigate real life experience and the emotions of asthmatic patients, highlighting unmet needs related to patient's experience of his/her disease that need to be included in severe asthmatics' management strategy.

Mepolizumab Improves Outcomes of Chronic Rhinosinusitis with Nasal Polyps in Severe Asthmatic Patients: A Multicentric Real-Life Study.

Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab's effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3, p < 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p < 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 ± 461.5 cell/µL; mean t12 blood eosinophils 107.5 ± 104.6 cell/µL, p < 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a "typical" responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations.

The Role of Blood Gas Analysis in the Post-Acute Phase of COVID-19 Pneumonia

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Post-tuberculosis lung disease: a comparison of Brazilian, Italian, and Mexican cohorts.

OBJECTIVE: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. METHODS: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. RESULTS: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. CONCLUSIONS: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.

Heart rate recovery in adult individuals with asthma.

Slow heart rate recovery (HRR) after exercise is a predictor of overall mortality in individuals with and without cardiovascular or respiratory disorders. No data on adults with asthma are available. The purpose of the study is to evaluate the prevalence of slow HRR in these individuals as compared with those with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of baseline characteristics and physiological response to the six-minute walking distance test of stable individuals with asthma or COPD. Slow HRR was defined as HRpeak - HR at 1 minute after end exercise <12 bpm. Individuals with asthma walked significantly longer (median (IQR): 455 (385-512) vs 427 (345-485) meters; p=0.005) with a lower prevalence of slow HRR (30.3% vs 49.0%, respectively: p<0.001) than those with COPD. Individuals with asthma and slow HRR were older and walked less than those with normal HRR, without any difference in airway obstruction or in disease severity. Multivariate analysis showed that only the difference HRpeak - baseline HR (∆HR), was a predictor of slow HRR in both groups. More than 30% of adult individuals with asthma may show slow HRR. Only exercise ∆HR but no baseline characteristic seems to predict the occurrence of slow HRR.

History of prevention, diagnosis, treatment and rehabilitation of pulmonary sequelae of tuberculosis.

Tuberculosis (TB), known as the White Plague' is of great significance to humanity for the magnitude of morbidity and mortality it has generated over centuries from the very start of human civilization. In this Review, we will describe the history of prevention (vaccination and management of TB infection), diagnosis, treatment and pulmonary rehabilitation of post-treatment sequelae. The article leads the reader through the main discoveries which paved the way to the modern approach to TB prevention and care. The history of Bacille Calmette-Guérin (BCG) vaccine and of the diagnosis and treatment of TB infection are presented, together with that of diagnosis and treatment of TB disease. Pivotal was in 1882 the discovery by Robert Koch of the aetiological agent of TB, and his pioneering work in culturing the bacillus and developing tuberculin. Also of enormous importance was, in 1895, the discovery of the X-rays by Wilhelm Conrad Röntgen, discovery which paved the way to the development of the modern imaging technologies. To complement this, the more recent history of rehabilitation of post-treatment sequelae is summarized, given the importance this issue has on patients' wellbeing and Quality of Life.

Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry.

BACKGROUND: It is uncertain whether exposure to renin-angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. METHODS: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. RESULTS: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). CONCLUSIONS: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19.