Thoracic Society of Australia and New Zealand position statement: The safe clinical use of sputum induction for bio-sampling of the lower airways in children and adults.

Sputum induction is widely used in clinical settings for collection of biological samples from the lower airways. However, in recent years sputum induction has been associated with serious adverse events and even death. This position statement was commissioned by the Thoracic Society of Australia and New Zealand to address major adverse events of two deaths associated with sputum induction that have occurred in Australia in 2021, and outlines best practice for the safe use of sputum induction. The statement resulted from systematic literature searches by a multi-disciplinary group including respiratory physicians, nurses and physiotherapists (paediatric and adults focused). Consumers had input to an advanced draft of the position statement. The position statement covers indications for sputum induction, informed consent, scope of practice of personnel administering the procedure, infection control considerations, details about the sputum induction procedure, safety considerations and risk assessment in clinical settings.

In tobacco smokers with respiratory symptoms, a dual bronchodilator did not reduce symptoms at 12 wk.

SOURCE CITATION: Han MK, Ye W, Wang D, et al. Bronchodilators in tobacco-exposed persons with symptoms and preserved lung function. N Engl J Med. 2022;387:1173-84. 36066078.

Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations. Purpose: To evaluate the comparative effectiveness and adverse events (AEs) of pharmacologic interventions for adults with exacerbation of COPD. Data Sources: English-language searches of several bibliographic sources from database inception to 2 January 2019. Study Selection: 68 randomized controlled trials that enrolled adults with exacerbation of COPD treated in out- or inpatient settings other than intensive care and compared pharmacologic therapies with placebo, "usual care," or other pharmacologic interventions. Data Extraction: Two reviewers independently extracted data and rated study quality and strength of evidence (SOE). Data Synthesis: Compared with placebo or management without antibiotics, antibiotics given for 3 to 14 days were associated with increased exacerbation resolution at the end of the intervention (odds ratio [OR], 2.03 [95% CI, 1.47 to 2.80]; moderate SOE) and less treatment failure at the end of the intervention (OR, 0.54 [CI, 0.34 to 0.86]; moderate SOE), independent of severity of exacerbations in out- and inpatients. Compared with placebo in out- and inpatients, systemic corticosteroids given for 9 to 56 days were associated with less treatment failure at the end of the intervention (OR, 0.01 [CI, 0.00 to 0.13]; low SOE) but also with a higher number of total and endocrine-related AEs. Compared with placebo or usual care in inpatients, other pharmacologic interventions (aminophyllines, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids, and short-acting bronchodilators) had insufficient evidence, showing either no or inconclusive effects (with the exception of the mucolytic erdosteine) or improvement only in lung function. Limitation: Scant evidence for many interventions; several studies had unclear or high risk of bias and inadequate reporting of AEs. Conclusion: Antibiotics and systemic corticosteroids reduce treatment failure in adults with mild to severe exacerbation of COPD. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018111609).

Improving Blood Pressure Management in Primary Care Patients with Chronic Kidney Disease: a Systematic Review of Interventions and Implementation Strategies.

INTRODUCTION: Chronic kidney disease (CKD) is widely prevalent, associated with morbidity and mortality, but may be lessened with timely implementation of evidence-based strategies including blood pressure (BP) control. Nonetheless, an evidence-practice gap persists. We synthesize the evidence for clinician-facing interventions to improve hypertension management in CKD patients in primary care. METHODS: Electronic databases and related publications were queried for relevant studies. We used a conceptual model to address heterogeneity of interventions. We conducted a quantitative synthesis of interventions on blood pressure (BP) outcomes and a narrative synthesis of other CKD relevant clinical outcomes. Planned subgroup analyses were performed by (1) study design (randomized controlled trials (RCTs) or nonrandomized studies (NRS)); (2) intervention type (guideline-concordant decision support, shared care, pharmacist-facing); and (3) use of behavioral/implementation theory. RESULTS: Of 2704 manuscripts screened, 73 underwent full-text review; 22 met inclusion criteria. BP target achievement was reported in 15 and systolic BP reduction in 6 studies. Among RCTs, all interventions had a significant effect on BP control, (pooled OR 1.21; 95% CI 1.07 to 1.38). Subgroup analysis by intervention type showed significant effects for guideline-concordant decision support (pooled OR 1.19; 95% CI 1.12 to 1.27) but not shared care (pooled OR 1.71; 95% CI 0.96 to 3.03) or pharmacist-facing interventions (pooled OR 1.04; 95% CI 0.82 to 1.34). Subgroup analysis finding was replicated with pooling of RCTs and NRS. The five contributing studies showed large and significant reduction in systolic BP (pooled WMD - 3.86; 95% CI - 7.2 to - 0.55). Use of a behavioral/implementation theory had no impact, while RCTs showed smaller effect sizes than NRS. DISCUSSION: Process-oriented implementation strategies used with guideline-concordant decision support was a promising implementation approach. Better reporting guidelines on implementation would enable more useful synthesis of the efficacy of CKD clinical interventions integrated into primary care. PROSPERO REGISTRATION NUMBER: CRD42018102441.

Diagnosis and treatment of lung disease associated with alpha one-antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand.

AATD is a common inherited disorder associated with an increased risk of developing pulmonary emphysema and liver disease. Many people with AATD-associated pulmonary emphysema remain undiagnosed and therefore without access to care and counselling specific to the disease. AAT augmentation therapy is available and consists of i.v. infusions of exogenous AAT protein harvested from pooled blood products. Its clinical efficacy has been the subject of some debate and the use of AAT augmentation therapy was recently permitted by regulators in Australia and New Zealand, although treatment is not presently subsidized by the government in either country. The purpose of this position statement is to review the evidence for diagnosis and treatment of AATD-related lung disease with reference to the Australian and New Zealand population. The clinical efficacy and adverse events of AAT augmentation therapy were evaluated by a systematic review, and the GRADE process was employed to move from evidence to recommendation. Other sections address the wide range of issues to be considered in the care of the individual with AATD-related lung disease: when and how to test for AATD, changing diagnostic techniques, monitoring of progression, disease in heterozygous AATD and pharmacological and non-pharmacological therapy including surgical options for severe disease. Consideration is also given to broader issues in AATD that respiratory healthcare staff may encounter: genetic counselling, patient support groups, monitoring for liver disease and the need to establish national registries for people with AATD in Australia and New Zealand.

Electronic cigarettes: A position statement from the Thoracic Society of Australia and New Zealand.

The TSANZ develops position statements where insufficient data exist to write formal clinical guidelines. In 2018, the TSANZ addressed the question of potential benefits and health impacts of electronic cigarettes (EC). The working party included groups focused on health impacts, smoking cessation, youth issues and priority populations. The 2018 report on the Public Health Consequences of E-Cigarettes from the United States NASEM was accepted as reflective of evidence to mid-2017. A search for papers subsequently published in peer-reviewed journals was conducted in August 2018. A small number of robust and important papers published until March 2019 were also identified and included. Groups identified studies that extended, modified or contradicted the NASEM report. A total of 3793 papers were identified and reviewed, with summaries and draft position statements developed and presented to TSANZ membership in April 2019. After feedback from members and external reviewers, a collection of position statements was finalized in December 2019. EC have adverse lung effects and harmful effects of long-term use are unknown. EC are unsuitable consumer products for recreational use, part-substitution for smoking or long-term exclusive use by former smokers. Smokers who require support to quit smoking should be directed towards approved medication in conjunction with behavioural support as having the strongest evidence for efficacy and safety. No specific EC product can be recommended as effective and safe for smoking cessation. Smoking cessation claims in relation to EC should be assessed by established regulators.

Association of Home Noninvasive Positive Pressure Ventilation With Clinical Outcomes in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Importance: The association of home noninvasive positive pressure ventilation (NIPPV) with outcomes in chronic obstructive pulmonary disease (COPD) and hypercapnia is uncertain. Objective: To evaluate the association of home NIPPV via bilevel positive airway pressure (BPAP) devices and noninvasive home mechanical ventilator (HMV) devices with clinical outcomes and adverse events in patients with COPD and hypercapnia. Data Sources: Search of MEDLINE, EMBASE, SCOPUS, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, National Guideline Clearinghouse, and Scopus for English-language articles published from January 1, 1995, to November 6, 2019. Study Selection: Randomized clinical trials (RCTs) and comparative observational studies that enrolled adults with COPD with hypercapnia who used home NIPPV for more than 1 month were included. Data Extraction and Synthesis: Data extraction was completed by independent pairs of reviewers. Risk of bias was evaluated using the Cochrane Collaboration risk of bias tool for RCTs and select items from the Newcastle-Ottawa Scale for nonrandomized studies. Main Outcomes and Measures: Primary outcomes were mortality, all-cause hospital admissions, need for intubation, and quality of life at the longest follow-up. Results: A total of 21 RCTs and 12 observational studies evaluating 51 085 patients (mean [SD] age, 65.7 [2.1] years; 43% women) were included, among whom there were 434 deaths and 27 patients who underwent intubation. BPAP compared with no device was significantly associated with lower risk of mortality (22.31% vs 28.57%; risk difference [RD], -5.53% [95% CI, -10.29% to -0.76%]; odds ratio [OR], 0.66 [95% CI, 0.51-0.87]; P = .003; 13 studies; 1423 patients; strength of evidence [SOE], moderate), fewer patients with all-cause hospital admissions (39.74% vs 75.00%; RD, -35.26% [95% CI, -49.39% to -21.12%]; OR, 0.22 [95% CI, 0.11-0.43]; P < .001; 1 study; 166 patients; SOE, low), and lower need for intubation (5.34% vs 14.71%; RD, -8.02% [95% CI, -14.77% to -1.28%]; OR, 0.34 [95% CI, 0.14-0.83]; P = .02; 3 studies; 267 patients; SOE, moderate). There was no significant difference in the total number of all-cause hospital admissions (rate ratio, 0.91 [95% CI, 0.71-1.17]; P = .47; 5 studies; 326 patients; SOE, low) or quality of life (standardized mean difference, 0.16 [95% CI, -0.06 to 0.39]; P = .15; 9 studies; 833 patients; SOE, insufficient). Noninvasive HMV use compared with no device was significantly associated with fewer all-cause hospital admissions (rate ratio, 0.50 [95% CI, 0.35-0.71]; P < .001; 1 study; 93 patients; SOE, low), but not mortality (21.84% vs 34.09%; RD, -11.99% [95% CI, -24.77% to 0.79%]; OR, 0.56 [95% CI, 0.29-1.08]; P = .49; 2 studies; 175 patients; SOE, insufficient). There was no statistically significant difference in the total number of adverse events in patients using NIPPV compared with no device (0.18 vs 0.17 per patient; P = .84; 6 studies; 414 patients). Conclusions and Relevance: In this meta-analysis of patients with COPD and hypercapnia, home BPAP, compared with no device, was associated with lower risk of mortality, all-cause hospital admission, and intubation, but no significant difference in quality of life. Noninvasive HMV, compared with no device, was significantly associated with lower risk of hospital admission, but there was no significant difference in mortality risk. However, the evidence was low to moderate in quality, the evidence on quality of life was insufficient, and the analyses for some outcomes were based on small numbers of studies.

Tuberculin Skin Test Conversions and Occupational Exposure Risk in US Healthcare Workers.

Background: Healthcare workers (HCWs) undergo occupational tuberculosis screening at regular intervals. However, the risk of contracting tuberculosis at the workplace in a setting with a low background tuberculosis incidence is unclear. We aimed to evaluate the risk of tuberculin skin test (TST) conversion and the risk of occupational tuberculosis infection among HCWs in such a setting. Methods: We conducted a retrospective cohort study of employees of a large tertiary medical center in the US Midwest who had undergone TST screening during the study period 1 January 1998 to 31 May 2014. Results: Among 40142 HCWs who received a TST, only 123 converted over 16.4 years. Only 9 (7%) of the converters had a suspected tuberculosis exposure at the workplace and none developed active tuberculosis. The majority of TST converters (66%) had a negative QuantiFERON-TB test at the time of the conversion. Conclusions: In one of the largest cohorts of HCWs in a low-tuberculosis-incidence setting, we demonstrated an extremely low risk of occupational tuberculosis exposure among TST converters and no resulting active tuberculosis cases. In this setting, the approach of testing HCWs at baseline and after tuberculosis exposure, rather than at regular intervals, should be considered.

Screening for tuberculosis in migrants and visitors from high-incidence settings: present and future perspectives.

In most settings with a low incidence of tuberculosis (TB), foreign-born people make up the majority of TB cases, but the distribution of the TB risk among different migrant populations is often poorly quantified. In addition, screening practices for TB disease and latent TB infection (LTBI) vary widely. Addressing the risk of TB in international migrants is an essential component of TB prevention and care efforts in low-incidence countries, and strategies to systematically screen for, diagnose, treat and prevent TB among this group contribute to national and global TB elimination goals.This review provides an overview and critical assessment of TB screening practices that are focused on migrants and visitors from high to low TB incidence countries, including pre-migration screening and post-migration follow-up of those deemed to be at an increased risk of developing TB. We focus mainly on migrants who enter the destination country via application for a long-stay visa, as well as asylum seekers and refugees, but briefly consider issues related to short-term visitors and those with long-duration multiple-entry visas. Issues related to the screening of children and screening for LTBI are also explored.

Noninvasive Ventilation in Patients With Do-Not-Intubate and Comfort-Measures-Only Orders: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the effectiveness of noninvasive ventilation in patients with acute respiratory failure and do-not-intubate or comfort-measures-only orders. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to January 1, 2017. STUDY SELECTION: Studies of all design types that enrolled patients in the ICU or hospital ward who received noninvasive ventilation and had preset do-not-intubate or comfort-measures-only orders. DATA EXTRACTION: Data abstraction followed Meta-analysis of Observational Studies in Epidemiology guidelines. Data quality was assessed using a modified Newcastle-Ottawa Scale. DATA SYNTHESIS: Twenty-seven studies evaluating 2,020 patients with do-not-intubate orders and three studies evaluating 200 patients with comfort-measures-only orders were included. In patients with do-not-intubate orders, the pooled survival was 56% (95% CI, 49-64%) at hospital discharge and 32% (95% CI, 21-45%) at 1 year. Hospital survival was 68% for chronic obstructive pulmonary disease, 68% for pulmonary edema, 41% for pneumonia, and 37% for patients with malignancy. Survival was comparable for patients treated in a hospital ward versus an ICU. Quality of life of survivors was not reduced compared with baseline, although few studies evaluated this. No studies evaluated quality of dying in nonsurvivors. In patients with comfort-measures-only orders, a single study showed that noninvasive ventilation was associated with mild reductions in dyspnea and opioid requirements. CONCLUSIONS: A large proportion of patients with do-not-intubate orders who received noninvasive ventilation survived to hospital discharge and at 1 year, with limited data showing no decrease in quality of life in survivors. Provision of noninvasive ventilation in a well-equipped hospital ward may be a viable alternative to the ICU for selected patients. Crucial questions regarding quality of life in survivors, quality of death in nonsurvivors, and the impact of noninvasive ventilation in patients with comfort-measures-only orders remain largely unanswered.

Risk of tuberculosis in patients with solid cancers and haematological malignancies: a systematic review and meta-analysis.

There is uncertainty regarding whether patients with cancer should be screened for latent tuberculosis infection (LTBI). We performed a systematic review and meta-analysis to estimate the relative incidence of tuberculosis (TB) in cancer.We searched MEDLINE and Embase for studies published before December 21, 2016. We included studies that evaluated the incidence of TB in patients with solid cancers and haematological malignancies relative to a reference group (study control or general population). A pooled estimate of the incidence rate ratio (IRR) was obtained using standard meta-analysis methods.The search strategy identified 13 unique studies including 921 464 patients with cancer. The IRR of TB for adult patients with cancer was 2.61 (95% CI 2.12-3.22; I2=91%). In haematological cancers, the IRR was 3.53 (95% CI 1.63-7.64; I2=96%); and in solid cancers in adults, it was 2.25 (95% CI 1.96-2.58; I2=91%). The highest IRR was found in children with haematological malignancies or solid cancers (IRR 16.82, 95% CI 8.81-32.12; I2=79%).Considering the limited duration of maximum immunosuppression in cancer and reduced cumulative lifetime risk of TB because of reduced life expectancy, children, but not adults, appear to be at a sufficient level of risk to warrant systematic screening for LTBI.

Interpreting diagnostic tests with continuous results and no gold standard: a common scenario explained using the tuberculin skin test.

Practitioners of evidence-based medicine commonly encounter diagnostic tests with continuous results and no gold standard. In contrast, the traditional critical appraisal teachings assume a binary test (2×2 table) with a gold standard. In this guide, we use the example of the tuberculin skin test to illustrate a simple approach facilitated by using stratum-specific likelihood ratios and odds of developing future patient-important events. This approach can aid practitioners in the interpretation and application of diagnostic tests to patient care.

Multidrug-Resistant Tuberculosis in Patients for Whom First-Line Treatment Failed, Mongolia, 2010-2011.

In Ulaanbaatar, Mongolia, multidrug-resistant tuberculosis (MDR TB) was diagnosed for more than a third of new sputum smear-positive tuberculosis patients for whom treatment had failed. This finding suggests a significant risk for community-acquired MDR TB and a need to make rapid molecular drug susceptibility testing available to more people.

Benefit of treatment of latent tuberculosis infection in individual patients.

We aimed to develop a decision aid that estimates whether treatment of latent tuberculosis infection (LTBI) is likely to have a net gain in quality-adjusted life-years for an individual. A Markov model was developed which incorporated personalised estimates for risk of tuberculosis (TB) reactivation, TB death, quality-of-life impairments and treatment side-effects. The net effect of LTBI treatment was quantified in terms of quality-adjusted life-years gained or lost. Analyses were conducted for a representative set of hypothetical patients. LTBI treatment was estimated to be beneficial when the annual risk of TB reactivation exceeded 13/100,000 to 93/100,000 for females aged 10-75 years and 15/100,000 to 119/100,000 for males aged 10-75 years; the numbers needed to treat to avoid one case of TB were 93, 77, 85 and 72, respectively, at these threshold levels. LTBI treatment was estimated to confer a positive net benefit across a broad range of patients with characteristics typically seen in a low incidence setting for TB. Use of the decision aid has the potential to facilitate and increase confidence with LTBI treatment decisions by providing clinicians and patients with personalised estimates of likely net benefit.

Community-based directly observed therapy (DOT) versus clinic DOT for tuberculosis: a systematic review and meta-analysis of comparative effectiveness.

BACKGROUND: Directly observed therapy (DOT), as recommended by the World Health Organization, is used in many countries to deliver tuberculosis (TB) treatment. The effectiveness of community-based (CB DOT) versus clinic DOT has not been adequately assessed to date. We compared TB treatment outcomes of CB DOT (delivered by community health workers or community volunteers), with those achieved through conventional clinic DOT. METHODS: We performed a systematic review and meta-analysis of studies before 9 July 2014 comparing treatment outcomes of CB DOT and clinic DOT. The primary outcome was treatment success; the secondary outcome was loss to follow-up. RESULTS: Eight studies were included comparing CB DOT to clinic DOT, one a randomised controlled trial. CB DOT outperformed clinic DOT treatment success (pooled odds ratio (OR) of 1.54, 95% confidence interval (CI) 1.01 - 2.36, p = 0.046, I(2) heterogeneity 84%). No statistically significant difference was found between the two DOT modalities for loss to follow-up (pooled OR 0.86, 95% CI 0.48 to 1.55, p = 0.62, I(2) 83%). CONCLUSIONS: Based on this systematic review, CB DOT has a higher treatment success compared to clinic DOT. However, as only one study was a randomised controlled trial, the findings have to be interpreted with caution.

Healthcare-associated pneumonia: a US disease or relevant to the Asia Pacific, too?

The term 'health care-associated pneumonia' (HCAP) was introduced by the American Thoracic Society and the Infectious Diseases Society of America in 2005 to describe a distinct entity of pneumonia that resembles hospital-acquired pneumonia rather than community-acquired pneumonia (CAP) in terms of occurrence of drug-resistant pathogens and mortality in patients that--while not hospitalized in the traditional sense--have been in recent contact with the health-care system. It was proposed that HCAP should be treated empirically with therapy for drug-resistant pathogens. Over the last few years, there has been increasing controversy over whether HCAP is a helpful definition, or leads to unnecessary and potentially problematic overtreatment. The term HCAP has been extensively criticized in Europe. While most studies have shown that HCAP is associated with more frequent drug-resistant pathogens and higher mortality than CAP, there is no clear evidence that this is due to inappropriate antibiotic therapy. Therapy consistent with HCAP treatment guidelines has also not been found to improve mortality. Based on current evidence, we suggest broad-spectrum antibiotic therapy to treat possible pathogens not usually covered in CAP be based on assessment of individual risk factors rather than applying a HCAP classification system in the Asia-Pacific Region.

Alignment of Doctors' Understanding of Treatment Burden Priorities and Chronic Heart Failure Patients' Experiences: A Nominal Group Technique Consultation.

Purpose: To identify and rank areas of treatment burden in chronic heart failure (CHF), including solutions, that should be discussed during the clinical encounter from a patient, and doctors' perspective. Patients and Methods: Patients with CHF and clinicians managing heart failure were invited. Nominal group technique sessions held either face to face or online in 2021-2022, with individual identification of priorities and voting on ranking. Results: Four patient groups (N=22) and one doctor group (N=5) were held. For patients with heart failure, in descending order of priority Doctor-patient communication, Inefficiencies of the healthcare system, Healthcare access issues, Cost implications of treatment, Psychosocial impacts on patients and their families, and Impact of treatment work were the most important treatment burdens. Priorities independently identified by the doctors aligned with the patients' but ranking differed. Patient solutions ranged from involvement of nurses or pharmacists to enhance understanding of discharge planning, through to linkage between health information systems, and maintaining strong family or social support networks. Doctors' solutions covered timing medicines with activities of daily living, patient education on the importance of compliance, medication reviews to overcome clinical inertia, and routine clinical audits. Conclusion: The top treatment burden priorities for CHF patients were related to interaction with clinicians and health system inefficiencies, whereas doctors were generally aware of patients' treatment burden but tended to focus on the complexity of the direct treatment work. Addressing the priority issues identified here can commence with clinicians becoming aware of the issues that matter to patients and proactively discussing feasible immediate and longer-term solutions during clinical encounters.