Alpha-1 deficiency in severe asthma patients.

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..

TB and interstitial lung disease: a systematic review and meta-analysis.

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..

Factors influencing delayed discharge after day-surgery laparoscopic cholecystectomy: the DeDiLaCo study protocol.

OBJECTIVE: Laparoscopic cholecystectomy (LC) is the gold standard for most benign gallbladder diseases. Early discharge (<24 hours) has the same outcomes as longer (>24 hours) hospital stay. Nevertheless, the rate of delayed discharge >24 hours range from 4.6% to 37%. The primary endpoint of this Italian nationwide study is to analyze the prevalence of patients undergoing elective LC who experienced a delayed discharge >24 hours and identify potential limiting factors of early discharge. Results from these analyses will be used to select patients who can be safely discharged on the same day after surgery. Secondary endpoints will be to evaluate the patient's quality of life (QoL), assess the direct health costs associated with late discharge, and quantify the patient's involvement in the treatment process. PATIENTS AND METHODS: This prospective, observational study was conducted following a resident-led model and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. All patients were treated according to the local hospital protocol and received routine care as standard therapy. RESULTS: We expected to obtain the enrollment of at least 500 patients based on an assumed difference in discharge delay between the reference and the recruitable population of 6% and the identification of factors related to discharge failure within 24 h. Early discharge after LC leads to advantages both in terms of clinical outcomes and quality of life of the patient, and it is highly effective in terms of health costs and shortening the waiting list. However, clinical reality differs from the results of randomized studies by a complex series of non-objectionable real-world data influencing treatment plans. Therefore, we expected to identify independent predictors and factors of failure of early discharge. CONCLUSIONS: Clinical reality often differs from randomized trial results. In Italy, the vast majority of delayed discharges after LC may not be related to surgery and can be prevented both with logistical reorganization and with a readjustment of the trust reimbursement policies.

Vaccination in post-tuberculosis lung disease management: A review of the evidence.

INTRODUCTION AND OBJECTIVES: Post-tuberculosis lung disease (PTLD), as other chronic respiratory disorders, may have infectious complications; some of them can be prevented with vaccinations. So far, no document has discussed the potential role of vaccination in PTLD. Therefore, the objective of this review was to describe vaccination recommendations to prevent infections potentially capable of complicating PTLD. MATERIALS AND METHODS: A non-systematic review of the literature was conducted. The following keywords were used: tuberculosis, vaccination, vaccines and PTLD. PubMed/MEDLINE and Embase were used as the search engine, focusing on English-language literature only. RESULTS: We identified 9 vaccines potentially useful in PTLD. Influenza, pneumococcal and anti-COVID-19 vaccinations should be recommended. Patients with PTLD can also benefit from vaccination against shingles. Vaccination against pertussis is mainly relevant during childhood. Diphtheria, tetanus and measles vaccination are recommended for general population and should be considered in patients with PTLD not previously vaccinated. Tdap (Tetanus, diphtheria, and pertussis) booster should be repeated in every adult every ten years. Vaccination against BCG retains its importance during early childhood in countries where TB is endemic. CONCLUSIONS: Vaccination deserves to be considered among the strategies to prevent and/or mitigate PTLD complications. Further evidence is necessary to better understand which vaccines have the greatest impact and cost-benefit.

Silicosis and tuberculosis: A systematic review and meta-analysis.

INTRODUCTION: Silicosis mostly happens in workers with high silica exposure and may accompany the development of various diseases like tuberculosis, cancer, or autoimmune diseases. The term silico-tuberculosis describes a condition in which an individual is affected by both silicosis and tuberculosis at the same time. This systematic review and meta-analysis study was conducted to evaluate the risk of tuberculosis in silicosis patients and individuals exposed to silica dust. METHODS: We performed a systematic search for relevant studies up to 6 September 2022 using PubMed/ Medline, and Embase with the following keywords in titles or abstracts: "silicosis" OR "silicoses" OR "pneumoconiosis" OR "pneumoconioses" AND "tuberculosis". Cohort and case-control studies containing relevant and original information about tuberculosis infection in silicosis patients were included for further analysis. Pooled estimates and 95% confidence intervals (CI) for the relative risk of tuberculosis in individuals with silicosis compared to those without; these were evaluated using the random effects model due to the estimated heterogeneity of the true effect sizes. RESULTS: Out of 5352 potentially relevant articles, 7 studies were eligible for systematic review, of which 4 cohort studies were included for meta-analysis. The total population of all studies was 5884, and 90.63% were male. The mean age of participants was 47.7 years. Our meta-analysis revealed a pooled risk ratio of 1.35 (95%CI 1.18-1.53, I 2: 94.30%) which means an increased risk of silicosis patients and silica-exposed individuals to tuberculosis infection. CONCLUSION: Silicosis and silica dust exposure increase the risk of tuberculosis. Therefore, we suggest that individuals with long-time silica exposure, like mine workers, be routinely considered for both silicosis and tuberculosis screening programs.

A systematic review of the costs of diagnosis for multidrug-resistant/extensively drug-resistant TB in different settings.

BACKGROUND: We performed an analysis of the cost and relative merits of different strategies for the diagnosis of multidrug-resistant/extensively drug-resistant TB (MDR/XDR-TB) in different settings.METHODS: We systematically reviewed the published evidence on cost/cost-effectiveness of rapid MDR/pre-XDR-TB and other methods for XDR-TB testing up to September 2022. PRISMA guidelines were followed. Collected data were analysed using Stata v17 software. Cost data were reported in USD ($) and summarised by mean, standard deviation, and range. Country income level was defined according to the World Bank country classification. Three simplified scenarios were also used to explore testing implications, based on low, intermediate and high TB incidence.RESULTS: Of 157 records, 25 studies were included with 24 reporting the cost of Xpert/RIF and two that evaluated the implementation of the MTBDRplus test. The total rapid test cost ranged from $12.41-$218, including $1.13-$74.60 for reagents/consumables and $0.40-$14.34 for equipment.CONCLUSION: The cost of MDR/XDR-TB diagnostics is lower in low resource settings. However, the cost-effective implementation of MDR/XDR-TB diagnostic algorithms requires careful consideration of local resources to avoid missed identification and the use of inappropriate regimen.

High-flow nasal cannula versus non-invasive ventilation for acute hypercapnic respiratory failure in adults: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Non-invasive ventilation (NIV) with bi-level positive pressure ventilation is a first-line intervention for selected patients with acute hypercapnic respiratory failure. Compared to conventional oxygen therapy, NIV may reduce endotracheal intubation, death, and intensive care unit length of stay (LOS), but its use is often limited by patient tolerance and treatment failure. High-flow nasal cannula (HFNC) is a potential alternative treatment in this patient population and may be better tolerated. RESEARCH QUESTION: For patients presenting with acute hypercapnic respiratory failure, is HFNC an effective alternative to NIV in reducing the need for intubation? METHODS: We searched EMBASE, MEDLINE, and the Cochrane library from database inception through to October 2021 for randomized clinical trials (RCT) of adults with acute hypercapnic respiratory failure assigned to receive HFNC or NIV. The Cochrane risk-of-bias tool for randomized trials was used to assess risk of bias. We calculated pooled relative risks (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with corresponding 95% confidence intervals (CI) using a random-effects model. RESULTS: We included eight RCTs (n = 528) in the final analysis. The use of HFNC compared to NIV did not reduce the risk of our primary outcome of mortality (RR 0.86, 95% CI 0.48-1.56, low certainty), or our secondary outcomes including endotracheal intubation (RR 0.80, 95% CI 0.46-1.39, low certainty), or hospital LOS (MD - 0.82 days, 95% CI - 1.83-0.20, high certainty). There was no difference in change in partial pressure of carbon dioxide between groups (MD - 1.87 mmHg, 95% CI - 5.34-1.60, moderate certainty). INTERPRETATION: The current body of evidence is limited in determining whether HFNC may be either superior, inferior, or equivalent to NIV for patients with acute hypercapnic respiratory failure given imprecision and study heterogeneity. Further studies are needed to better understand the effect of HFNC on this population.

Infections in lung transplanted patients: A review.

Lung transplantation can improve the survival of patients with severe chronic pulmonary disorders. However, the short- and long-term risk of infections can increase morbidity and mortality rates. A non-systematic review was performed to provide the most updated information on pathogen, host, and environment-related factors associated with the occurrence of bacterial, fungal, and viral infections as well as the most appropriate therapeutic options. Bacterial infections account for about 50% of all infectious diseases in lung transplanted patients, while viruses represent the second cause of infection accounting for one third of all infections. Almost 10% of patients develop invasive fungal infections during the first year after lung transplant. Pre-transplantation comorbidities, disruption of physical barriers during the surgery, and exposure to nosocomial pathogens during the hospital stay are directly associated with the occurrence of life-threatening infections. Empiric antimicrobial treatment after the assessment of individual risk factors, local epidemiology of drug-resistant pathogens and possible drug-drug interactions can improve the clinical outcomes.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Bronchoscopic sampling techniques in the era of technological bronchoscopy.

Flexible bronchoscopy is a key diagnostic and therapeutic tool. New endoscopes and technologically advanced navigational modalities have been recently introduced on the market and in clinical practice, mainly for the diagnosis of mediastinal lymph adenopathies and peripheral lung nodules. Bronchoscopic sampling tools have not changed significantly in the last three decades, with the sole exception of cryobiopsy. We carried out a non-systematic, narrative literature review aimed at summarizing the scientific evidence on the main indications/contraindications, diagnostic yield, and safety of the available bronchoscopic sampling techniques. Performance of bronchoalveolar lavage, bronchial washing, brushing, forceps biopsy, cryobiopsy and needle aspiration techniques are described, focusing on indications and diagnostic accuracy in the work-up of endobronchial lesions, peripheral pulmonary abnormalities, interstitial lung diseases, and/or hilar-mediastinal lymph adenopathies. Main factors affecting the diagnostic yield and the navigational methods are evaluated. Preliminary data on the utility of the newest sampling techniques (i.e., new needles, triple cytology needle brush, core biopsy system, and cautery-assisted transbronchial forceps biopsy) are shown. TAKE HOME MESSAGE: A deep knowledge of bronchoscopic sampling techniques is crucial in the era of technological bronchoscopy for an optimal management of respiratory diseases.

Therapeutic strategies and outcomes of MDR and pre-XDR-TB in Italy: a nationwide study.

BACKGROUND: Treatment outcomes in multidrug-resistant TB (MDR-TB) patients are suboptimal in several low-incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18-year period. Secondary outcomes were treatment outcomes in certain drug-containing regimens and the possibility for the WHO shorter MDR-TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug-resistance patterns were found: MDR-TB in 68.6%, pre-extensively drug-resistant TB (pre-XDR-TB) in 30.4% and XDR-TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR- (68.8%) and pre-XDR-TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR-TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR- and pre-XDR-TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.

Minimal clinically important difference of the 6-min walking test in patients with asthma.

BACKGROUND: The 6-min walking test (6MWT) is responsive to physiological changes and pulmonary rehabilitation (PR) in patients with asthma. The minimal clinically important difference (MCID) has not been established yet.OBJECTIVE: To determine the MCID of 6MWT in patients with asthma.METHODS: Using the perceived change in walking ability and the modified Medical Research Council (mMRC) score as anchors, receiver operating characteristic curves and quantile regression, we evaluated 6MWT before and after PR in these patients. The St George Respiratory Questionnaire (SGRQ), the COPD assessment test (CAT) and other outcome measures were also assessed.RESULTS: Of 142 patients with asthma, 37 were enrolled. After PR, 6MWT increased from 453.4 m ± 88.8 to 493.0 m ± 97.2 (P = 0.0001); other outcome measures also increased. There was a slight correlation between baseline 6MWT and SGRQ, CAT and mMRC. No significant correlations were found between post-PR changes in 6MWT and in other outcome measures. Comparing different methods of assessment, the MCID ranged from 26 m to 27 m.CONCLUSION: The most conservative estimate of the MCID of 6MWT after PR was 26 m in patients with asthma. This estimate may be useful in clinical interpretation of data, particularly in response to intervention studies.

TB management in the European Union/European Economic Area: a multi-centre survey.

BACKGROUND: Essential TB care in the European Union/European Economic Area (EU/EEA) comprises 21 standards for the diagnosis, treatment and prevention of TB that constitute the European Union Standards for Tuberculosis Care (ESTC).METHODS: In 2017, we conducted an audit on TB management and infection control measures against the ESTC standards. TB reference centres in five EU/EEA countries were purposely selected to represent the heterogeneous European TB burden and examine geographic variability.RESULTS: Data from 122 patients, diagnosed between 2012 and 2015 with multidrug-resistant TB (n = 49), extensively drug-resistant TB (XDR-TB) (n = 11), pre-XDR-TB (n = 29) and drug-susceptible TB (n = 33), showed that TB diagnosis and treatment practices were in general in agreement with the ESTC.CONCLUSION: Overall, TB management and infection control practices were in agreement with the ESTC in the selected EU/EEA reference centres. Areas for improvement include strengthening of integrated care services and further implementation of patient-centred approaches.

Tuberculosis and COVID-19 interaction: A review of biological, clinical and public health effects.

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 studied Similarly, 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.