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.

A case of severe Mycobacterium thermoresistibile pneumonia.

Mycobacterium thermoresistibile is a thermotolerant nontuberculous mycobacterium which can rarely result in human infection. Although immunosuppression has been identified as a risk factor for infection, it is possible that mycobacterial laboratories may have previously under-recognized M. thermoresistibile as standard mycobacterial incubation temperatures are suboptimal for culture of this organism. Here, we present a case of severe M. thermoresistibile pneumonia associated with achalasia requiring life support in the intensive care unit. We speculated that the interplay between specific host and environmental risk factors contributed to acquisition of infection. Infection with this fastidious organism required prolonged treatment with multiple antimicrobials and adjunctive therapeutic drug monitoring which led to clinical cure despite residual lung injury. We also reviewed literature documenting cases of human infection with M. thermoresistibile. The diagnosis of M. thermoresistibile requires a high degree of clinical suspicion considering its association with immunosuppressive conditions, postulated environmental inoculation and eponymous culture growth characteristics.

Tuberculosis, focussed tools and the right schools: estimated impact and cost of a targeted student screening programme for tuberculosis infection.

BACKGROUND: The World Health Organization (WHO) recommends targeted screening for latent tuberculosis infection (LTBI) among high-risk populations. Recent studies that evaluate targeted school-based programmes in low burden settings are scarce. AIMS: To evaluate a school screening programme for recently arrived migrant students from moderate and high tuberculosis (TB) burden countries and estimate (1) the number of cases of active TB that were prevented and (2) the cost per case of active TB prevented. METHODS: Students were screened with tuberculin skin tests (TST) at schools with a high migrant population intake. Those with positive results were referred for specialist evaluation. Outcomes were retrospectively assessed using 5 years of prospectively collected data. Cost data were collected. Main outcomes measured were the number of children were diagnosed with LTBI who completed treatment, and programme costs. RESULTS: Of 4728 student screened, 295 (6.2%) were diagnosed with LTBI. Of these, 273 (92.5%) were offered preventive therapy, 242 (82.0%) commenced and 204 (69.2%) completed therapy. The number needed to screen (NNS) was 23 per completed course of preventive treatment for LTBI. Assuming a 10% lifetime risk of reactivation, the NNS was 386 per case of TB disease notification avoided. The cost of screening was A$23 932 per case of TB disease avoided. CONCLUSIONS: This TB strategy is supported by the high rate of TB infection in the student group, the treatment uptake and completion rates. Cost-benefit is linked with lifetime risk of TB reactivation. Targeted school screening programmes represent an important opportunity for TB control in low-burden settings.

Image-guided percutaneous biopsy and pathological diagnosis in atypical tuberculous spondylitis: a case series and clinical outcomes.

Background: Tuberculous spondylitis can be difficult to distinguish from alternative spinal pathologies such as malignancy, particularly if the imaging features are not typical. Biopsy and histopathological analysis are facilitative to the early and accurate diagnosis of atypical tuberculous spondylitis and the clinical management. The purpose of this study is to describe some of the atypical imaging features of tuberculous spondylitis diagnosed by image-guided percutaneous biopsy, as well as associated treatment outcomes. Methods: We performed a retrospective analysis of all patients diagnosed with tuberculous spondylitis after image-guided percutaneous biopsy at The Third Affiliated Hospital of Southern Medical University between 2013 and 2020. Of the patients identified, those with atypical imaging features were selected for case review. All patients were given anti-tuberculous medication treatment with or without surgery. The imaging features, histological and microbiological results, and clinical presentations and outcomes were evaluated. Neurological function was evaluated according to the Frankel grading system. The clinical outcomes were evaluated by Visual Analogic Scale (VAS) scores for pain, imaging [X-ray, computed tomography (CT), and magnetic resonance imaging (MRI)] results, and laboratory examinations. Comparison of VAS scores was made by Student t-test. Results: Of the 102 patients identified with tuberculous spondylitis between 2013 and 2020, eight patients (two females and six males) with a mean age of 41.6 years (range, 18-61 years) demonstrated atypical imaging findings, including central vertebral body lesion, multiple skip vertebral lesions, extradural mass lesion and anterior subperiosteal lesion. All eight patients received anti-tuberculous medication treatment, and six underwent surgery. One patient developed a pleural effusion after debridement of the thoracic lesion. The mean follow-up period was 16.2 months (6-37 months). The VAS scores before treatment and at the final follow-up showed significant differences (7.25±1.49 and 0.0±0.0, respectively, P<0.01). Improved neurological function were observed in all patients. Solid fusion and osteogenic osteosclerosis were observed at the final follow-up, and no recurrence was observed in any cases. Conclusions: All eight patients had a good prognosis. Image-guided biopsy and histopathological analysis are helpful for the early diagnosis of tuberculous spondylitis, especially when imaging features are not typical for this condition.

Pulmonary AL amyloidosis and multiple myeloma presenting as cough with diffuse pulmonary opacities.

Amyloidosis is an uncommon multisystem disease that can affect many organs. However, interstitial lung involvement is very rare. A 68-year-old man presented with long-standing dyspnoea and productive cough. After extensive investigation, including two non-diagnostic bronchoscopies, a surgical lung biopsy demonstrated pulmonary amyloidosis. A bone marrow biopsy confirmed multiple myeloma. The patient was treated with chemotherapy and an autologous stem cell transplant.

Centralised versus outreach models of cystic fibrosis care should be tailored to the needs of the individual patient.

Cystic fibrosis (CF) is a common life-limiting genetic condition. As the disease progresses access to specialist tertiary multi-disciplinary care services may become necessary. For patients living in regional/remote Australia, accessing such services may be a challenge. Here, we describe long-term outcomes for CF patients according to their access to specialist CF centre care in childhood.

Within-Host Evolution of Burkholderia pseudomallei during Chronic Infection of Seven Australasian Cystic Fibrosis Patients.

Cystic fibrosis (CF) is a genetic disorder characterized by progressive lung function decline. CF patients are at an increased risk of respiratory infections, including those by the environmental bacterium Burkholderia pseudomallei, the causative agent of melioidosis. Here, we compared the genomes of B. pseudomallei isolates collected between ~4 and 55 months apart from seven chronically infected CF patients. Overall, the B. pseudomallei strains showed evolutionary patterns similar to those of other chronic infections, including emergence of antibiotic resistance, genome reduction, and deleterious mutations in genes involved in virulence, metabolism, environmental survival, and cell wall components. We documented the first reported B. pseudomallei hypermutators, which were likely caused by defective MutS. Further, our study identified both known and novel molecular mechanisms conferring resistance to three of the five clinically important antibiotics for melioidosis treatment. Our report highlights the exquisite adaptability of microorganisms to long-term persistence in their environment and the ongoing challenges of antibiotic treatment in eradicating pathogens in the CF lung. Convergent evolution with other CF pathogens hints at a degree of predictability in bacterial evolution in the CF lung and potential targeted eradication of chronic CF infections in the future.IMPORTANCEBurkholderia pseudomallei, the causative agent of melioidosis, is an environmental opportunistic bacterium that typically infects immunocompromised people and those with certain risk factors such as cystic fibrosis (CF). Patients with CF tend to develop chronic melioidosis infections, for reasons that are not well understood. This report is the first to describe B. pseudomallei evolution within the CF lung during chronic infection. We show that the pathways by which B. pseudomallei adapts to the CF lung are similar to those seen in better-studied CF pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia complex species. Adaptations include the accumulation of antibiotic resistance, loss of nonessential genes, metabolic alterations, and virulence factor attenuation. Known and novel mechanisms of resistance to three of the five antibiotics used in melioidosis treatment were identified. Similar pathways of evolution in CF pathogens, including B. pseudomallei, provide exciting avenues for more-targeted treatment of chronic, recalcitrant infections.

The changing prevalence of pulmonary infection in adults with cystic fibrosis: A longitudinal analysis.

BACKGROUND: Increased patient longevity and aggressive antibiotic treatment are thought to impact on the microbial composition of the airways of adults with cystic fibrosis (CF). In this study, we sought to determine if a temporal change in the airway microbiology of adults with CF has occurred over time. METHODS: Longitudinal analysis of sputum microbiology results was undertaken on patients attending a large adult CF centre. Clinical status and health outcomes of transitioning patients were also assessed. RESULTS: A decrease in the prevalence of Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia complex and Aspergillus spp. (p=0.001, p<0.001, p=0.002 and p<0.001, respectively) occurred. Improvements in lung function among transitioning patients infected with P. aeruginosa were observed. CONCLUSION: Overtime, a decline in the prevalence of many CF airway pathogens has occurred. Significantly, an incremental improvement in lung function was reported for transitioning patients with current P. aeruginosa infections.

Long-term safety of tiotropium delivered by Respimat® SoftMist™ Inhaler: patient selection and special considerations.

Tiotropium bromide is a long-acting inhaled muscarinic antagonist used in patients with chronic respiratory disease. It has been available since 2002 as a single-dose dry powder formulation via the HandiHaler® dry powder inhaler (DPI) device, and since 2007 as the Respimat® SoftMist™ Inhaler (SMI). The latter is a novel method of medication delivery that utilizes a multidose aqueous solution to deliver the drug as a fine mist. Potential benefits include more efficient drug deposition throughout the respiratory tract, reduced systemic exposure, and greater ease of use and patient satisfaction compared with the use of HandiHaler DPI. Although tiotropium bromide delivered via the HandiHaler DPI has been clearly shown to improve lung function, dyspnea, and quality of life and to reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), there is accumulating evidence regarding the use of tiotropium HandiHaler in other respiratory diseases characterized by airflow limitation, such as asthma and cystic fibrosis. Developed more recently, tiotropium delivered via the Respimat SMI appears to have a similar efficacy and safety profile to the HandiHaler DPI, and early data raising the possibility of safety concerns with its use in COPD have been refuted by more recent evidence. The benefits over the HandiHaler DPI, however, remain unclear. This paper will review the evidence for tiotropium delivered via the Respimat SMI inhaler, in particular as an alternative to the HandiHaler DPI, and will focus on the safety profile for each of the chronic lung diseases in which it has been trialed, as well as an approach to appropriate patient selection.

An international, multicentre evaluation and description of Burkholderia pseudomallei infection in cystic fibrosis.

BACKGROUND: Several cases of Burkholderia pseudomallei infection in CF have been previously reported. We aimed to identify all cases globally, risk factors for acquisition, clinical consequences, and optimal treatment strategies. METHODS: We performed a literature search to identify all published cases of B. pseudomallei infection in CF. In addition we hand-searched respiratory journals, and contacted experts in infectious diseases and CF around the world. Supervising clinicians for identified cases were contacted and contemporaneous clinical data was requested. RESULTS: 25 culture-confirmed cases were identified. The median age at acquisition was 21 years, mean FEV1 % predicted was 60 %, and mean BMI was 19.5 kg/m(2). The location of acquisition was northern Australia or south-east Asia for most. 19 patients (76 %) developed chronic infection, which was usually associated with clinical decline. Successful eradication strategies included a minimum of two weeks of intravenous ceftazidime, followed by a consolidation phase with trimethoprim/sulfamethoxazole, and this resulted in a higher chance of success when instituted early. Three cases of lung transplantation have been recorded in the setting of chronic B. pseudomallei infection. CONCLUSION: Chronic carriage of B. pseudomallei in patients with CF appears common after infection, in contrast to the non-CF population. This is often associated with an accelerated clinical decline. Lung transplantation has been performed in select cases of chronic B. pseudomallei infection.

Utility of EBUS-TBNA for diagnosis of mediastinal tuberculous lymphadenitis: a multicentre Australian experience.

BACKGROUND: Endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) is an important diagnostic procedure for the interrogation of mediastinal lymph nodes. There is limited data describing the accuracy & safety of this technique for the diagnosis of tuberculous mediastinal lymphadenitis. METHODS: A multi-centre retrospective study of all EBUS-guided TBNA procedures that referred samples for mycobacteriology was performed. Results were correlated with post-procedural diagnoses after a period of surveillance and cross-checked against relevant statewide tuberculosis (TB) registries, and sensitivity and specificity was calculated. In addition, nucleic acid amplification techniques (NAAT) were assessed, and sensitivity and specificity calculated using positive mycobacterial culture as the reference gold standard. RESULTS: One hundred and fifty-nine patients underwent EBUS-TBNA and had tissue referred for mycobacterial culture, of which 158 were included in the final analysis. Thirty-nine were ultimately diagnosed with TB (25%). Sensitivity of EBUS-TBNA for microbiologically confirmed tuberculous mediastinal lymphadenitis was 62% (24/39 cases). Specificity was 100%. Negative predictive value (NPV) and diagnostic accuracy for microbiologic diagnosis was 89% [95% confidence intervals (CI), 82-93%] and 91% (95% CI, 84-94%) respectively. For a composite clinicopathologic diagnosis of TB NPV and accuracy were 98% (95% CI, 93-99%) and 98% (95% CI, 95-99%) respectively. Sensitivity for NAAT was 38% (95% CI, 18-65%). CONCLUSIONS: EBUS-TBNA is a safe and well tolerated procedure in the assessment of patients with suspected isolated mediastinal lymphadenitis and demonstrates good sensitivity for a microbiologic diagnosis of isolated mediastinal lymphadenitis. When culture and histological results are combined with high clinical suspicion, EBUS-TBNA demonstrates excellent diagnostic accuracy and NPV for the diagnosis of mediastinal TB lymphadenitis. We suggest EBUS-TBNA should be considered the procedure of choice for patients in whom TB is suspected.

Indacaterol, a once-daily beta2-agonist, versus twice-daily beta2-agonists or placebo for chronic obstructive pulmonary disease.

BACKGROUND: Indacaterol is an inhaled long-acting beta2-agonist that is administered once daily and has been investigated as a treatment for chronic obstructive pulmonary disease (COPD). Four different doses have been investigated (75 mcg, 150 mcg, 300 mcg and 600 mcg). The relative effects of different doses of once-daily indacaterol in the management of patients with COPD are uncertain. OBJECTIVES: To compare the efficacy and safety of indacaterol versus placebo and alternative twice-daily long-acting beta2-agonists for the treatment of patients with stable COPD. SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), handsearched respiratory journals and meeting abstracts and searched the Novartis trials registry and ClinicalTrials.gov. The date of the most recent search was 8 November 2014. SELECTION CRITERIA: We included all randomised controlled trials comparing indacaterol at any dose versus placebo or alternative long-acting beta2-agonists. Trials were required to be of at least 12 weeks' duration and had to include adults older than 18 years with a confirmed spirometric diagnosis of COPD. DATA COLLECTION AND ANALYSIS: Two review authors (JBG, EJD) independently assessed for possible inclusion all citations identified as a result of the search. Disagreements were resolved through discussion or, if required, through resolution by a third review author (RWB). One review author (JBG) extracted data from trials identified by the search and entered these data into Review Manager 5.1 for statistical analysis. Data entry was cross-checked by a second review author (EJD, CJC). MAIN RESULTS: A total of 13 trials with 9961 participants were included in the review. Ten trials with a total of 8562 participants involved an indacaterol versus placebo comparison. Five trials with a total of 4133 participants involved an indacaterol versus twice-daily beta2-agonist comparison. The comparator beta2-agonists were salmeterol, formoterol and eformoterol. One of these trials, with a total of 90 participants, provided no data that could be used in this review. Two trials included both indacaterol versus placebo and indacaterol versus twice-daily beta2-agonist comparisons. Trials were between 12 weeks and 52 weeks in duration. Overall the quality of the evidence was strong, and risk of significant bias was minimal in most of the included studies. Enrolled participants had stable COPD across a range of spirometric severities. Forced expiratory volume in 1 second (FEV1) was generally between 30% and 80% predicted, and a mean FEV1 of approximately 50% was predicted in most studies. Patients with concurrent respiratory disease, including asthma, were excluded. Concomitant use of inhaled corticosteroids was permitted.The primary objectives were to compare trough FEV1 at the end of dosing, exacerbation rates and quality of life. Significant adverse events, mortality and dyspnoea were included as secondary outcomes. Compared with placebo, a significant and clinically relevant improvement in trough FEV1 was noted with indacaterol (mean difference (MD) 149.11, 95% confidence interval (CI) 137.09 to 161.12). In addition, compared with placebo, a significant improvement in mean St George Respiratory Questionaire (SGRQ) score (MD -3.60, 95% CI -4.36 to -2.83) was reported, and the proportion of participants experiencing clinically relevant improvement in SGRQ score was significantly greater (odds ratio (OR) 1.63, 95% CI 1.46 to 1.84). Compared with twice-daily beta2-agonists, a small but statistically significant increase in trough FEV1 was seen with indacaterol (MD 61.71 mL, 95% CI 41.24 to 82.17). Differences between indacaterol and twice-daily beta2-agonists in mean SGRQ scores (MD -0.81, 95% CI -2.28 to 0.66) and in the proportions of participants achieving clinically relevant improvements in SGRQ scores (OR 1.07, 95% CI 0.87 to 1.32) were not statistically significant, but the confidence intervals are too wide to permit the conclusion that the treatments were equivalent. Data were insufficient for analysis of differences in exacerbation rates for both placebo and twice-daily beta2-agonist comparisons. AUTHORS' CONCLUSIONS: For patients with stable COPD, use of indacaterol versus placebo results in statistically significant and clinically meaningful improvements in lung function and quality of life. The clinical benefit for lung function is at least as good as that seen with twice-daily long-acting beta2-agonists. The comparative effect on quality of life remains uncertain, as important differences cannot be excluded.

Pregnancy and cystic fibrosis: Approach to contemporary management.

Over the previous 50 years survival of patients with cystic fibrosis has progressively increased. As a result of improvements in health care, increasing numbers of patients with cystic fibrosis are now considering starting families of their own. For the health care professionals who look after these patients, the assessment of the potential risks, and the process of guiding prospective parents through pregnancy and beyond can be both challenging and rewarding. To facilitate appropriate discussions about pregnancy, health care workers must have a detailed understanding of the various important issues that will ultimately need to be considered for any patient with cystic fibrosis considering parenthood. This review will address these issues. In particular, it will outline pregnancy outcomes for mothers with cystic fibrosis, issues that need to be taken into account when planning a pregnancy and the management of pregnancy for mothers with cystic fibrosis or mothers who have undergone organ transplantation as a result of cystic fibrosis.

Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome in a 26-year-old woman with cystic fibrosis: a case report.

INTRODUCTION: The microangiopathic hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is a rare and potentially fatal complication of pregnancy. Here, to the best of our knowledge, we describe only the second reported case of this syndrome in a woman with cystic fibrosis. CASE PRESENTATION: This report describes the case of a 26-year-old woman of Caucasian ethnicity with mild cystic fibrosis bronchiectasis who ultimately manifested the triad of microangiopathic hemolysis, elevated liver enzymes, and low platelet count in the third trimester of pregnancy. Her baby was delivered successfully after a semi-elective caesarean section. CONCLUSIONS: Pregnancies in patients with cystic fibrosis are associated with an increased rate of complications. This case is of importance as it describes only for the second time the successful delivery of a baby in a women with cystic fibrosis, in a pregnancy also threatened by the microangiopathic hemolysis, elevated liver enzymes, and low platelet syndrome. This case will be of special interest to obstetricians, pediatricians, and medical, nursing and allied health staff involved in the delivery of cystic fibrosis care.

Acute spontaneously resolving pulmonary vasculitis: a case report.

This is the first description that we are aware of describing the spontaneous resolution of an acute pulmonary vasculitis, possibly secondary to microscopic polyangiitis. Haemoptysis is a common symptom for patients presenting to primary and tertiary referral centres, and pulmonary vasculitis is one of a variety of aetiologies that should always be considered. The pulmonary vasculitides are difficult diagnostic and management problems. They are encumbered by a relative paucity of level 1 evidence addressing their diagnosis, classification, and treatment. This is therefore an important paper to publish because it adds to the global breadth of experience with this important clinical condition.