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It is now well understood that the effect of TB does not always end when a patient completes a successful course of treatment. Successful treatment is by definition a microbiological cure, but people may continue to suffer the consequences of TB for months or years after treatment. For example, ongoing health challenges can present in the form of post-TB lung disease (PTLD), and there is a high incidence of TB-related symptoms associated with disability in other domains. We discuss an article in this issue of the Journal that explores the experiences of adult TB survivors, which further expands our understanding of this condition.

BACKGROUND: In 2022, 11 of 22 Member States of the WHO Eastern Mediterranean Region (EMR) had an estimated TB incidence of 80% when consolidating the responses, reaching sufficient from all domains. Two reached

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis.The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally.This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year.All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines.Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10–80% in the remaining 5 countries).The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3−7) in the overall cohort and 6 (4−8) among patients with a final outcome).For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13−23) (in days 553 (385–678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30−90) days for the whole cohort and 60 (30−100) for patients with a final outcome and, respectively, of 55 (30−90) and 60 (30−90) days for culture conversion.Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Evidence is accumulating on the interaction between tuberculosis (TB) and COVID-19.The aim of the present review is to report the available evidence on the interaction between these two infections. Differences and similarities of TB and COVID-19, their immunological features, diagnostics, epidemiological and clinical characteristics and public health implications are discussed. The key published documents and guidelines on the topic have been reviewed.Based on the immunological mechanism involved, a shared dysregulation of immune responses in COVID-19 and TB has been found, suggesting a dual risk posed by co-infection worsening COVID-19 severity and favouring TB disease progression.The available evidence on clinical aspects suggests that COVID-19 happens regardless of TB occurrence either before, during or after an active TB diagnosis. More evidence is required to determine if COVID-19 may reactivate or worsen active TB disease. The role of sequeale and the need for further rehabilitation must be further studiedSimilarly, the potential role of drugs prescribed during the initial phase to treat COVID-19 and their interaction with anti-TB drugs require caution. Regarding risk of morbidity and mortality, several risk scores for COVID-19 and independent risk factors for TB have been identified: including, among others, age, poverty, malnutrition and co-morbidities (HIV co-infection, diabetes, etc.). Additional evidence is expected to be provided by the ongoing global TB/COVID-19 study.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts.Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality.Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%).Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B.Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27–49) VS. 66 (46–70) years, whereas in cohort B 37 (27–46) VS. 48 (47–60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26–19.2%) natives; p-value: 0.005).The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

Tuberculosis (TB) in migrants represents an important clinical and public health threat, particularly in low TB incidence countries. The current review is aimed to assess issues related to screening and treatment of migrants with latent TB infection or TB disease. Keywords: TB migrants, TB elimination, TB control screening

The goals of the End TB strategy, which aims to achieve a 90% reduction in tuberculosis (TB) incidence and a 95% reduction in TB mortality by 2035, will not be achieved without new tools to fight TB. These include improved point of care (POC) diagnostic tests that are meant to be delivered at the most decentralised levels of care where the patients make the initial contact with the health system, as well as within the community. These tests should be able to be performed on an easily accessible sample and provide results in a timely manner, allowing a quick treatment turnaround time of a few minutes or hours (in a single clinical encounter), hence avoiding patient loss-to-follow-up. There have been exciting developments in recent years, including the WHO endorsement of Xpert MTB/RIF, Xpert MTB/RIF Ultra, loop-mediated isothermal amplification (TB-LAMP) and lateral flow lipoarabinomannan (LAM). However, these tests have limitations that must be overcome before they can be optimally applied at the POC. Furthermore, worrying short- to medium-term gaps exist in the POC diagnostic test development pipeline. Thus, not only is better implementation of existing tools and algorithms needed, but new research is required to develop new POC tests that allow the TB community to truly make an impact and find the “missed TB cases”. Keywords: Tuberculosis, Point-of-care, Diagnosis, Target product profile, Xpert, LAM, NAATs

The risk of exposure, progression to active tuberculosis (TB) and then to cure is a process affected by several risk factors. Along with well known risk factors such as human immunodeficiency virus (HIV), use of immunosuppressive drugs and being of young age, emerging risk factors such socio-economic and behavioral aspects play a significant role in increasing the susceptibility to infection, and unsuccessful treatment outcomes. This paper summarizes the effects of these socio-economic determinants and co-morbidities (including HIV) on TB infection and disease. Keywords: Tuberculosis, Socio-economic determinants, HIV, Poverty, Alcohol, Tobacco, Homeless, Malnutrition, Undernutrition, Overcrowding

Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). However, it is not known to what extent DM affects the outcome in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) treated with second-line anti-TB drugs.The objective of this study was to compare the microbiological evolution (sputum smear and culture conversion) and final outcomes of MDR/XDR-TB patients with and without DM, managed at the national TB reference centre in Mexico City. Results: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (e.g. MDR-TB with additional resistance to one injectable drug or a fluoroquinolone, 12.2%) and 6 (6.7%) with XDR-TB. Out of these, 49 (54.4%) had DM and 42 (86%) were undergoing insulin treatment.No statistically significant differences were found in treatment outcomes comparing DM vs. non-DM MDR-TB cases: 18/32 (56.3%) of DM cases and 19/24 (79.2%) non DM patients achieved treatment success (p = 0.07). The time to sputum smear and culture conversion was longer (although not statistically) in patients without DM, as follows: the mean (±SD) time to sputum smear conversion was 53.9 (±31.4) days in DM patients and 65.2 (±34.8) days in non-DM ones (p = 0.15), while the time to culture conversion was 66.2 (±27.6) days for DM and 81.4 (±37.7) days for non-DM MDR-TB cases (p = 0.06). Conclusions: The study results support the Mexican National TB programme to strengthen its collaboration with the DM programme, as an entry point for TB (and latent TB infection) screening and management. Keywords: Diabetes mellitus, Delay, Sputum and culture conversion, MDR-TB, High treatment adherence

Evidence on effectiveness, safety, and tolerability of imipenem/clavulanate (IC) and linezolid containing regimens to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is scarce. The aim of this observational study is to evaluate the therapeutic contribution of IC and linezolid to manage MDR/XDR-TB cases at the reference centre of São Paulo state, Brazil. Twelve patients (9 males, 1 HIV positive in antiretroviral treatment, 4 MDR, 8 XDR) were treated with IC, 11 of them within linezolid-containing regimens. They all were previously treated with treatment failure, for a median (IQR, interquartile range) of 4.5 (2â6.5) times, having a severe resistance pattern (median number of resistances: 7 (5â8)) and being sputum smear and culture positive. IC and linezolid were prescribed at the dose of 1000 mg/day and 600 mg/day, respectively. The overall exposure was (median (IQR)) 419 (375.5â658) days for IC and 678 (392â720) days for linezolid. All of them converted their sputum (time to sputum conversion; 60 (37.5â90) days) and culture (75 (60â135) days), and 7 were cured while 5 are still on treatment with a gradually improving clinical picture.While no adverse events were reported for IC, 2 minor side effects, only, were attributed to linezolid (17%); in both cases the drug was re-started without further problems. Our study suggests that IC and linezolid-containing regimens can be used safely and with satisfactory outcomes in reference centres to treat MDR/XDR-TB patients. Keywords: MDR-TB, XDR-TB, Imipenem, Linezolid, Effectiveness, Safety, Tolerability

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population., Methods: We conducted a systematic review and individual participant data meta-analysis. Databases were searched from Oct 1, 2014, to March 30, 2020. To be eligible, studies must have included more than five children or adolescents (0-19 years of age) treated for microbiologically confirmed or clinically diagnosed MDR or RR tuberculosis within a defined treatment cohort, and reported on regimen composition and treatment outcomes. Abstracts were screened independently by two authors to identify potentially eligible records. Full texts were reviewed by two authors independently to identify studies meeting the eligiblity criteria. For studies meeting eligiblity criteria, anonymised individual patient data was requested and individiual level data included for analysis. The main outcome assessed was treatment outcome defined as treatment success (cure or treatment completed) versus unfavourable outcome (treatment failure or death). Multivariable logistic regression models were used to identify associations between clinical and treatment factors and treatment outcomes. This study is registered with Prospero (CRD42020187230)., Findings: 1417 studies were identified through database searching. After removing duplicates and screening for eligibility, the search identified 23 369 individual participants from 42 studies, mostly from India and South Africa. Overall, 16 825 (72·0%) were successfully treated (treatment completed or cured), 2848 died (12·2%), 722 (3·1%) had treatment failure, and 2974 (12·7%) were lost to follow-up. In primary analyses, the median age was 16 (IQR 13-18) years. Of the 17 764 (87·1%) participants with reported HIV status, 2448 (13·8%) were living with HIV. 17 707 (89·6%) had microbiologically confirmed tuberculosis. After adjusting for significant factors associated with treatment outcome, the use of two (adjusted odds ratio [OR] 1·41 [95% CI 1·09-1·82]; p=0·008) or three (2·12 [1·61-2·79]; p<0·0001) WHO-classified group A drugs (bedaquiline, moxifloxacin, levofloxacin, and linezolid) compared with the use of no group A drugs at all was positively associated with treatment success., Interpretation: Younger and clinically diagnosed children are underrepresented among those treated for MDR and RR tuberculosis and should be a focus for case-finding efforts. Overall treatment outcomes in our analysis were better than in adults but lower than the international targets of 90% or more individuals successfully treated. Treatment with more group A drugs was associated with better treatment outcomes in children and adolescents, highlighting the need for more rapid access to these drugs and improved regimens., Funding: Unitaid., Competing Interests: Declaration of interests AJG-P reports that his institution receives grant funding from the US National Institutes of Health (NIH) and Unitaid for paediatric studies of bedaquiline, delamanid, pretomanid, clofazimine, moxifloxacin, and levofloxacin. J-JY reports donations of linezolid (Zyvox) from Pfizer, Delamanid (Deltyba) from Otsuka Pharmaceutical, and Rifampicin (Rifampcin) from Yuhan for the for the clinical trials, in which he served as a principal investigator. JF reports grant funding form the Stop TB Partnership's Global Drug Facility. JRC reports grant funding to his institution from the Canadian Institutes of Health, Fonds de recherche du Quebec-Sante, the National Sanatorium Association, and WHO; and consulting fees from WHO, the World Bank, and the Saskatchewan Auditors Office. BSG reports grant funding from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain). GEV reports grant funding from the NIH, US Agency for International Development (USAID), Unitaid, Medecins Sans Frontiers, and Partners in Health; and consulting fees from the Gates Medical Research Institute. RS reports grant funding from the NIH, the Bill and Melinda Gates Foundation, USAID, and from UNITE4TB (Academia and Industry United Innovation and Treatment for Tuberculosis). AS reports participating at the Research Lead at UK Academics and Professionals to end Tuberculosis. All other authors declare no competing interests., (Copyright © 2025 World Health Organization. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Introduction: As the COVID-19 pandemic transitions, understanding the intricate dynamics of the disease becomes paramount. This systematic review explores the role of antiphospholipid antibodies in COVID-19, focusing on their potential clinical implications., Methods: This systematic review, following PRISMA guidelines, assesses studies exploring the link between antiphospholipid antibodies and COVID-19. PubMed/Medline, Embase, and Scopus were searched for relevant studies published up to December 22, 2024. Inclusion criteria comprised studies involving patients diagnosed with COVID-19 and reporting on the presence of antiphospholipid antibodies. The risk of bias in individual studies was evaluated using the Joanna Briggs Institute appraisal tool., Results: Our Study includes 59 records involving a total of 28,489 COVID-19 patients. Antiphospholipid antibodies were tested in 14,498 COVID-19 patients. It was observed that 50.84% of patients tested positive for antiphospholipid antibodies. Various types of antiphospholipid antibodies, including Anticardiolipin, Anti beta2 glycoproteins, and Lupus anticoagulant antibody, displayed prevalence rates in the patients with thrombosis. The overall frequency of antiphospholipid antibodies in thrombosis patients was 38.55%., Conclusion: The presence of antiphospholipid antibodies in a significant proportion of COVID-19 patients underscores the need for a detailed investigation into their role in thrombotic events. Our study highlights potential avenues for targeted interventions. However, the evolving nature of COVID-19 necessitates continued research efforts to clarify clinical implications and optimize management strategies in this complex landscape of thrombosis and immunology. The review reveals some limitations, such as variability in study designs and demographics and inherent differences in methodologies among included studies. Future studies should address these limitations with standardized methodologies for more conclusive findings., (© 2025 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

A large number of people worldwide grapple with Major Depressive Disorder (MDD), and a significant portion of them confront resistance to conventional antidepressant treatments. Esketamine, an innovative intervention, has garnered attention due to its rapid-acting antidepressant effects. This meta-analysis aimed to evaluate the efficacy and safety of esketamine in individuals with MDD and Treatment-Resistant Depression (TRD). We performed an extensive search of electronic databases, including PubMed, EMBASE, and Cochrane Library, covering the period from inception to January 15, 2024, to identify clinical trials investigating the efficacy, safety, and tolerability of esketamine in individuals with MDD and TRD. Meta-analyses were conducted using a random-effect model, with the risk ratio (RR) chosen as the effect size. After screening, nine studies met inclusion criteria comprising 1752 patients. Esketamine dosages varied from 28 to 84 mg, administered intranasally in conjunction with an oral antidepressant. Intranasal esketamine exhibited significantly higher remission rates compared to the placebo (RR = 1.371, 95% CI: 1.194 to 1.574, p < 0.0001). Subgroup analysis revealed that the 84 mg and flexible doses were particularly effective. Moreover, intranasal esketamine demonstrated higher response rates compared to the placebo (RR = 1.274, 95% CI: 1.108 to 1.465, p-value = 0.001). Although adverse events were common in the esketamine group, they were generally tolerable. Intranasal esketamine demonstrated effectiveness in reducing scores among patients with MDD and TRD. The drug exhibited both safety and tolerability. However, further research is warranted to investigate its long-term effects and efficacy in specific patient subgroups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Tuberculosis (TB) risk associated with tumor necrosis factor-alpha (TNF-α) antagonist therapy in patients with autoimmune diseases is a significant concern. This study aims to evaluate the risk of TB disease associated with TNF-α antagonist therapy., Methods: An extensive search of PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL databases was conducted to identify randomized controlled trials (RCTs) assessing TB disease risk in patients receiving TNF-α antagonist therapy available until November 1, 2024. The pooled statistic used was the weighted odds ratio (OR) and a corresponding 95 % confidence interval (CI). Statistical analysis was performed using Comprehensive Meta-Analysis software, version 3.0 (Biostat Inc., Englewood, NJ, USA)., Results: Fifty-six RCTs, totaling 22,212 adult patients, met the specified eligibility criteria. Pooled analysis revealed an increased risk of TB disease associated with TNF-α antagonist therapy (OR 1.52, 95 % CI 1.03-2.26, p = 0.03). Subgroup analyses indicated a higher risk in patients with rheumatoid arthritis (RA) (OR 2.25, 95 % CI 1.13-4.45, p = 0.02), while no significant associations were found in patients with ankylosing spondylitis (AS) or psoriasis (Ps). Analyses by specific TNF-α antagonist drugs did not yield significant associations with risk of TB disease., Conclusion: Our study highlights an increased risk of TB disease associated with TNF-α antagonist therapy, particularly in patients with RA. However, the absence of significant associations in AS or Ps patients suggests disease-specific variations in risk of TB disease. Further research is needed to elucidate the long-term safety profile of TNF-α antagonist drugs and their associations with risk of TB disease in different patient populations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: Asthma is a chronic inflammatory respiratory disease often associated with comorbidities. Among cardiovascular comorbidities, arterial hypertension seems to create an additional health burden in asthmatics. However, evidence on this relationship is lacking., Objective: Our study aims to evaluate the characteristics of hypertensive asthmatics, focusing on the role of inflammation as a possible link between these diseases., Methods: We conducted a monocentric retrospective analysis consecutively including asthmatics who underwent induced sputum (IS) at our asthma referral center. Patients were divided in two groups according to presence or absence of history of hypertension. Clinical, functional, and inflammatory (airway and systemic) data were collected., Results: Data on two hundred and sixty asthmatic patients were analyzed. Seventy-nine (30.4%) of them had a diagnosis of hypertension requiring a specific pharmacological treatment. Asthmatics with hypertension were more frequently male ( p  = 0.047), older ( p  < 0.001), and with higher body max index (BMI) (p < 0.001) when compared to normotensive patients. No difference concerning asthma control, severity and pharmacological treatment was observed between the two groups (all p  > 0.05); distribution of comorbidities and lung function impairment (forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC); all p  < 0.05) were statistically different between groups. Mixed granulocytic airway inflammation was prevalent in the hypertensive asthmatics ( p  = 0.014). Interestingly, a multivariable analysis revealed that age ≥ 65 years and an increased percentage of sputum neutrophils (≥61%) were independent predictors of hypertensive status ( p  < 0.001)., Conclusion: Our data suggest that neutrophilic airway inflammation (as evaluated by induced sputum) is strictly associated with hypertension. In clinical practice, phenotyping asthmatic patients with comorbidities like hypertension could be useful also from a therapeutic point of view. Additional studies are mandatory to further elucidate the role of neutrophilic airway inflammation in asthma with cardiovascular diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Visca, Ardesi, Zappa, Pignatti, Grossi, Vanetti, Migliori, Centis, Angeli and Spanevello.)

Objective: Many biologic agents cause some degree of immunosuppression, which can increase the risk of reactivation of tuberculosis infection (TBI). This risk is variable between individual biologics. We aimed to assess current (and recommended) clinical practice of TBI screening and treatment among patients initiating treatment with biologic agents., Methods: An online questionnaire was distributed via email to members of the Global Tuberculosis Network and associated professional organisations to seek insights into the screening for and treatment of TBI in patients treated with biologics., Results: A total of 163 respondents in 27 countries answered at least one question. For all biologics described in the questionnaire, respondents advised increasing screening relative to current practice. Observed and supported TBI screening rates in patients treated with TNF-a inhibitors were high, especially for older TNF-a inhibitors. Most participants supported TBI screening in patients treated with B- or T-cell inhibitors but not in those treated with interleukin inhibitors. Guideline awareness was higher for TNF-a inhibitors than for other biologic classes (79% vs. 34%)., Conclusions: Although respondents stated that TBI screening rates are lower than what they consider ideal, there was a tendency to recommend TBI screening in patients treated with biologics not known to be associated with an increased risk of TBI. As a result, there is a potential risk of over-screening and over-treatment of TBI, potentially causing harm, in patients treated with biologics other than TNF-a inhibitors. There is a need to research the risk of TBI associated with biologics and for guidelines to address the spectrum of TBI risk across all types of biologics.

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 FEV 1 /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) FEV 1 , 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 FEV 1 /FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils., (© 2024. The Author(s).)

Alpha-1 antitrypsin (AAT) deficiency, an autosomal co-dominant condition, decreases protein concentration and activity at both serum and tissue levels. Few studies investigated whether the type of SERPINA1 gene phenotype in patients with severe asthma can influence symptoms and disease control during follow-up.To assess whether the presence of a non-MM genotype of SERPINA1 in patients with severe asthma is associated with disease control, systemic and airway inflammation, lung function and comorbidities prevalence compared to severe asthma patients with a homozygous genotype (MM).Asthmatic patients belonging to Global Initiative for Asthma (GINA) step 5 were retrospectively analysed in an Italian reference asthma clinic. We collected clinical, biological and functional variables at baseline and for the three following years.Out of 73 patients enrolled, 14 (19.18%) were non-MM and 59 (80.8%) were MM. Asthmatics with non-MM genotype had lower serum AAT concentration ( P = 0.004) and higher emphysema prevalence than the MM group ( P = 0.003) at baseline. During follow up, only MM patients showed a significant improvement of both ACQ-6 score ( P < 0.0001) and eosinophilic systemic inflammation ( P < 0.0001).Our findings emphasise the importance of a screening for AAT deficiency in severe asthma, as alleles mutation may influence patient's follow-up..

To determine the frequency of TB among patients with interstitial lung diseases (ILDs).We performed a comprehensive search in the PubMed/Medline, EMBASE and Scopus databases up to 1 August 2023 of studies reporting on the prevalence of TB among patients with ILDs.Twelve studies comprising 3,817 patients with ILD were found: the pooled prevalence of TB among ILD patients was 11.0% (95% CI 5.4-21.0). In the subgroup analysis, the TB rate among patients with silicosis and idiopathic pulmonary fibrosis (IPF) was respectively 35.6% (95% CI 32.6-38.8) and 4.4% (95% CI 3.6-5.3) ( P = 0.00). The frequency of TB among ILD patients was higher in high TB burden countries than in low/intermediate-burden countries: 26.3%, 95% CI 17.7-37.3 vs. 4.9%, 95% CI 3.3-7.2; P = 0.00.This study shows the frequency of TB among ILD patients. The meta-analysis reveals a significantly increased prevalence of TB among ILD patients with silicosis compared to IPF, and among individuals in high TB burden countries than in those with low/intermediate burden. The study results can help physicians and policymakers make efficient decisions for prompt screening and anti-TB treatment initiation in ILD patients..

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 FEF 25%-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.

Introduction: Osteoporosis poses a significant health concern, especially for individuals with chronic kidney disease (CKD). CKD disrupts mineral and bone metabolism, heightening the risk of fractures and complicating the management of osteoporosis. While anti-osteoporotic interventions aim to address bone health in CKD patients, ongoing research is essential to understand the comparative efficacy and safety of these medications, particularly in different CKD stages, notably in stages 4 and 5., Methods: We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials assessing the efficacy and safety of osteoporosis interventions in CKD up to June 15, 2024. The analysis utilized the pooled odds ratio (OR) along with the corresponding 95% confidence interval (CI), employing Comprehensive Meta-Analysis software, version 3.0. To assess heterogeneity in the results of individual studies, we used Cochran's Q statistic and the I2 statistic., Results: We analyzed 12 randomized controlled trials involving 31,027 participants, revealing a significantly lower risk of vertebral fractures with anti-osteoporotic agents (teriparatide, denosumab, romosozumab, raloxifene) compared to placebo (pooled OR, 0.28 [95% CI, 0.22-0.36]). Stratification by CKD stages showed a lower risk in Stages 1-3 but no significant reduction in stages 4 and 5. Teriparatide, denosumab, and romosozumab were effective in lowering fracture risk, whereas Raloxifene showed no significant effect. The lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (denosumab, raloxifene, risedronate, alendronate, teriparatide) and placebo. However, romosozumab demonstrated a significantly greater BMD change in all kidney function categories. No reported side effects were observed in CKD stages 1-5 across the trials., Conclusions: Our meta-analysis highlights the effectiveness of anti-osteoporotic agents in lowering vertebral fracture risk in CKD patients, particularly in stages 1-3. However, this benefit is not apparent in stages 4 and 5, necessitating further research. Despite the absence of reported side effects in CKD patients, clinicians should carefully assess the suitability of these medications, considering individual risks and benefits., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19., Methods: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both., Results: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53)., Conclusions: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2023.)

(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.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease. METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement). RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session. CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs). METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards. RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available. CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.