Safety of delivering bronchial thermoplasty in two treatment sessions.

BACKGROUND: Bronchial thermoplasty (BT) is a novel endoscopic therapy for severe asthma. Traditionally it is performed in three separate treatment sessions, targeting different portions of the lung, and each requires an anaesthetic and hospital admission. Compression of treatment into 2 sessions would present a more convenient alternative for patients. In this prospective observational study, the safety of compressing BT into two treatment sessions was compared with the traditional 3 treatment approach. METHODS: Sixteen patients meeting ERS/ATS criteria for severe asthma consented to participate in an accelerated treatment schedule (ABT), which treated the whole left lung followed by the right lung four weeks later. The short-term outcomes of these patients were compared with 37 patients treated with conventional BT scheduling (CBT). The outcome measures used to assess safety were (1) the requirement to remain in hospital beyond the electively planned 24-h admission and (2) the need for re-admission for any cause within of 30 days of treatment. RESULTS: The total number of radiofrequency activations delivered in the ABT group was similar to CBT (187 ± 21 vs 176 ± 40, p = 0.326). With ABT, 11 in 31 admissions (37.9%) required prolonged admission due to wheezing, compared to 5.4% with CBT (p = 0.0025). The mean hospital length of stay with ABT was 1.8 ± 1.3 days, compared to 1.1 ± 0.4 days (p < 0.001). ICU monitoring was required on 5 occasions with ABT (16.1%), compared to 0.9% with CBT (p = 0.002). Subgroup analysis demonstrated that females were more likely to require prolonged admission (OR 11.6, p = 0.0025). The 30-day hospital readmission rate was similar for both groups (6.4% vs 5.4%, p = 0.67). All patients made a complete recovery after treatment with similar outcomes at the 6-month follow-up reassessment. CONCLUSION: This study demonstrates that ABT results in greater short-term deterioration in lung function associated with a greater risk of prolonged hospital and ICU stay, predominantly affecting females. Therefore, in females, these risks need to be balanced against the convenience of fewer treatment sessions. In males, it may be an advantage to compress treatment.

Bronchial thermoplasty versus mepolizumab: Comparison of outcomes in a severe asthma clinic.

BACKGROUND AND OBJECTIVE: BT and interleukin-blocking monoclonal antibodies are both effective therapies for severe asthma, but there have been no direct comparisons between the two treatments. The aim of this study was to compare the efficacy and safety of BT and mepolizumab, in a real-world setting. METHODS: Patients with severe asthma despite optimized inhaler therapy were drawn from a severe asthma clinic in a tertiary hospital. Every patient commencing therapy with BT or mepolizumab was prospectively included in a national registry. At predetermined assessment points over a 12-month period, assessments were made of ACQ, spirometry, oral corticosteroid requiring exacerbations, reliever medication and maintenance oral corticosteroid use. RESULTS: A total of 91 patients with severe asthma participated: mean ACQ score 3.5 ± 1.0, FEV1 51.4 ± 17.7%, maintenance oral steroids 48.3% and 11.5 ± 10.0 inhalations/day reliever therapy. Forty-seven patients received mepolizumab and 44 received BT. Baseline characteristics were similar except significantly higher blood eosinophil count in the mepolizumab group. At 12 months, there were no differences between treatment outcomes for ACQ (1.9 ± 1.3 mepolizumab vs 1.7 ± 1.3 BT), exacerbation rate (0.9 ± 1.1 vs 0.9 ± 1.5), reduction in reliever use (-6.3 ± 10.5 vs -5.0 ± 8.8 puffs/day) or reduction in oral corticosteroids (-3.3 ± 7.5 vs - 5.8 ± 6.7 mg/day). The FEV1 improved equally (160 ± 290 vs 150 ± 460 mL). Readmission or prolonged admission was observed in 18.2% of BT patients, whilst 25.5% of mepolizumab patients had discontinued treatment at 12 months, 14.9% due to an adverse event or non-compliance. CONCLUSION: The results suggest that BT is as efficacious as mepolizumab for the treatment of severe asthma.

Safety and Effectiveness of Bronchial Thermoplasty When FEV1 Is Less Than 50.

BACKGROUND: Randomized clinical trials of bronchial thermoplasty (BT) were conducted in patients with a baseline FEV1 greater than 50%. There is a paucity of data regarding BT in patients with more severe obstruction, and consequently these patients are often excluded from receiving BT. The purpose of this study was to compare safety and efficacy outcomes in a large cohort of patients with an FEV1 less than 50% with those of a cohort of less obstructed patients. METHODS: Consecutive patients with severe asthma were drawn from the Australian BT Registry. Patients were grouped into (1) those with a baseline prebronchodilator FEV1 % predicted < 50% (n = 32) or (2) those with an FEV1 ≥ 50% (n = 36). Adverse outcomes were defined as (1) remaining in hospital longer than the planned 24-hour admission posttreatment or (2) being readmitted to hospital for any cause within 30 days of a treatment. Efficacy outcomes were evaluated 6 months after BT. RESULTS: More severely obstructed patients were no more likely to have experienced any adverse event. Significant improvements in Asthma Control Questionnaire score, exacerbation frequency, reliever medication use, and requirement for daily oral steroids were observed in both groups, and were of a similar degree. CONCLUSIONS: This study demonstrates that BT can confidently be offered to patients with asthma with an FEV1 that is 30% to 50% of predicted without risk of more frequent or more severe adverse events, and with the expectation of the same degree of response as patients with better lung function.

Hospitalised exacerbations of chronic obstructive pulmonary disease: adherence to guideline recommendations in an Australian teaching hospital.

BACKGROUND: Optimal management of exacerbations of chronic obstructive pulmonary disease (COPD) reduces patient morbidity and healthcare system burden. COPD guidelines, including the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and the COPD-X Plan, provide evidence-based recommendations, but adherence in hospital practice is variable. AIMS: To examine current practice in management of COPD exacerbations at an Australian teaching hospital and to compare with COPD-X Plan recommendations. METHODS: Data were collected retrospectively from electronic medical records for admissions occurring during 1 May to 31 August 2016, and compared with recommendations from the COPD-X Plan. RESULTS: A total of 134 patients (n = 68 females) was admitted for a COPD exacerbation during the study period. Mean age was 75.4 ± 10.2 years and 33.6% were current smokers. Airflow obstruction on spirometry was confirmed in 67.2% (mean forced expiratory volume in 1 s was 53 ± 22% predicted (1.2 ± 0.5 L)). Excellent adherence to the COPD-X Plan was demonstrated in the ordering of chest radiographs (97%) and electrocardiograms (94%). Supplemental oxygen was appropriately provided to all patients with oxygen saturation of <88%. All patients with confirmed hypercapnic respiratory failure were managed with non-invasive ventilation. Corticosteroids and bronchodilators were prescribed for the majority of patients. Areas of suboptimal practice included inadequate usage of arterial blood gases, excess supplemental oxygen in the absence of hypoxaemia, over-prescription of intravenous antimicrobials, low referral rates to pulmonary rehabilitation and insufficient smoking cessation counselling. CONCLUSIONS: Level of adherence to guideline recommendations in the management of COPD exacerbations is inadequate and further strategies are required to elevate standards of practice.

Predicting the Response to Bronchial Thermoplasty.

BACKGROUND: Although it is established that not all patients respond to bronchial thermoplasty (BT), the factors that predict response/nonresponse are largely unknown. OBJECTIVES: To identify baseline factors that predict clinical response. METHODS: The records of 77 consecutive patients entered into the Australian Bronchial Thermoplasty Registry were examined for baseline clinical characteristics, and outcomes measured at 6 and 12 months after BT, such as change in the Asthma Control Questionnaire (ACQ) score, exacerbation frequency, the requirement for short-acting beta-2 agonist (SABA) medication and oral corticosteroids, and improvement in spirometry. RESULTS: This was a cohort of patients with severe asthma: aged 57.7 ± 11.4 years, 57.1% females, 53.2% of patients taking maintenance oral steroids, 43% having been treated with an mAb, mean FEV1 of 55.8% ± 19.8% predicted. RESULTS: BT resulted in an improvement in the ACQ score from 3.2 ± 1.0 at baseline to 1.6 ± 1.1 at 6 months (P < .001). Exacerbation frequency in the previous 6 months reduced from 3.7 ± 3.3 to 0.7 ± 1.2 (P < .001). SABA requirement reduced from 9.3 ± 7.1 puffs/d to 3.5 ± 6.0 (P < .001), and 48.8% of patients were weaned completely off oral steroids. A significant improvement in FEV1 was observed. Using multiple linear regression models, baseline ACQ score strongly predicted improvement in ACQ score (P < .001). Patients with an exacerbation frequency greater than twice in the previous 6 months showed the greatest reduction in exacerbations (-5.3 ± 2.8; P < .001). Patients using more than 10 puffs/d of SABA experienced the greatest reduction in SABA requirement (-12.4 ± 10.5 puffs, P < .001). CONCLUSIONS: The most severely afflicted patients had the greatest improvements in ACQ score, exacerbation frequency, and medication requirement.

Airway smooth muscle as an underutilised biomarker: a case report.

BACKGROUND: Severe asthma and chronic obstructive pulmonary disease (COPD) can be challenging to manage, particularly when the clinical features may be similar. With the increased availability of advanced therapies for both entities, it is more important than ever to diagnose and phenotype accurately to inform appropriate treatment decisions. This case highlights the use of endobronchial biopsies to allow for histological evaluation of airways disease, and in particular the role of airway smooth muscle mass as an additional biomarker that could facilitate the diagnostic process. CASE PRESENTATION: A 65 year old woman presented with a diagnosis of severe COPD on the background of previous smoking and mild childhood asthma. Despite taking maximal inhaled pharmacotherapy, she had frequent exacerbations requiring corticosteroids and remained dyspnoeic on mild exertion. Lung function tests showed severe obstruction on spirometry (forced expiratory ratio 43%, forced expiratory volume in 1 s 47% predicted), and single breath Diffusing Capacity for Carbon Monoxide was moderately reduced at 45% predicted. Computed tomography revealed hyperinflation without marked emphysema. Quantitative CT for emphysema distribution demonstrated a relatively small lung fraction of 9.35% with <- 950 Hounsfield units. Bronchoscopy with endobronchial biopsy was undertaken to further determine the underlying pathology, and airway mucosa histology was consistent with typical findings of asthma. The patient was treated with bronchial thermoplasty as she did not meet prescribing criteria for monoclonal antibodies. Six months post treatment, she had a significant improvement in symptom control and medication usage, without any exacerbations. CONCLUSIONS: Airway smooth muscle histology is an underutilised biomarker that has a valuable role in phenotyping airways disease in the era of individualised medicine.

Measuring the effects of bronchial thermoplasty using oscillometry.

BACKGROUND AND OBJECTIVE: Bronchial thermoplasty (BT) has been consistently shown to reduce symptoms, exacerbations and the need for reliever medication in patients with severe asthma. Paradoxically, no consistent improvement in spirometry has been demonstrated. It has been suggested that this is due to a reduction in peripheral resistance in small airways, not captured by spirometry. Therefore, in this study, we evaluate the response to BT using oscillometry. METHODS: A total of 43 patients with severe asthma from two centres were evaluated at baseline, 6 weeks and 6 months post BT, using spirometry, plethysmography and oscillometry, in addition to medication usage, exacerbation frequency and the Asthma Control Questionnaire (5-item version) (ACQ-5). RESULTS: The mean age was 58.4 ± 11.2 years, forced expiratory volume in 1 s (FEV1 ) 55.5 ± 20.1% predicted, forced expiratory ratio 53.0 ± 14.5% and FEV1 response to salbutamol was 14.0 ± 14.5%. Following BT, the group responded to treatment with an improvement in ACQ-5 from 2.9 ± 0.9 at baseline to 1.7 ± 1.1 at 6 months (P < 0.005). There was an 81% reduction in exacerbation frequency (P < 0.001) and 50% of patients were weaned completely from maintenance oral corticosteroids. No changes after treatment were observed in spirometry but the residual volume reduced from 147 ± 38% to 139 ± 39% predicted (P < 0.01). Baseline oscillometry demonstrated high levels of resistance at 5 Hz with normal resistance at 20 Hz, indicating resistance in the small airways was elevated, but no changes were observed in any oscillometry parameter after BT treatment. CONCLUSION: Lung impedance measured with oscillometry did not change following BT despite marked clinical improvements in patients with severe asthma.

Bronchial thermoplasty: activations predict response.

BACKGROUND: Bronchial thermoplasty (BT) is an emerging bronchoscopic intervention for the treatment of severe asthma. The predictive factors for clinical response to BT are unknown. We examined the relationship between the number of radiofrequency activations applied and the treatment response observed. METHODS: Data were collected from 24 consecutive cases treated at three Australian centres from June 2014 to March 2016. The baseline characteristics were collated along with the activations delivered. The primary response measure was change in the Asthma Control Questionnaire-5 (ACQ-5) score measured at 6 months post BT. The relationship between change in outcome parameters and the number of activations delivered was explored. RESULTS: All patients met the ERS/ATS definition for severe asthma. At 6 months post treatment, mean ACQ-5 improved from 3.3 ± 1.1 to 1.5 ± 1.1, p < 0.001. The minimal clinically significant improvement in ACQ-5 of ≥0.5 was observed in 21 out of 24 patients. The only significant variable that differed between the 21 responders and the three non-responders was the number of activations delivered, with 139 ± 11 activations in the non-responders, compared to 221 ± 45 activations in the responders (p < 0.01). A significant inverse correlation was found between change in ACQ-5 score and the number of activations, r = -0.43 (p < 0.05). CONCLUSIONS: The number of activations delivered during BT has a role in determining clinical response to treatment.

Bronchial thermoplasty in severe asthma in Australia.

BACKGROUND: Bronchial thermoplasty (BT) is an approved bronchoscopic intervention for the treatment of severe asthma. However, limited published experience exists outside of clinical trials regarding patient selection and outcomes achieved. AIMS: To evaluate the effectiveness and safety of BT in patients with severe asthma encountered in clinical practice. METHODS: This is a retrospective analysis of the first 'real world' data from Australia. The following outcomes were measured prior to, and 6 months following BT: spirometry, Asthma Control Questionnaire-5 (ACQ-5) score, reliever and preventer medication use and exacerbation history. RESULTS: Twenty patients were treated from June 2014 to December 2015 at three university teaching hospitals. All subjects met the European Respiratory Society/American Thoracic Society definition of severe asthma. Mean pre-bronchodilator forced expiratory volume in 1 s was 62.8 ± 16.6% predicted (range: 33-95%). All patients were being treated with high dose inhaled corticosteroids, long-acting beta2 agonists and long-acting muscarinic antagonists. Ten patients (50%) were taking maintenance oral prednisolone. Most subjects also required at least one of montelukast (65%), omalizumab (30%) and methotrexate (20%). ACQ-5 improved from 3.6 ± 1.1 at baseline to 1.6 ± 1.2 at 6 months, P < 0.001. Short-acting reliever use decreased from a median of 8.0-0.25 puffs/day, P < 0.001, and exacerbations requiring corticosteroids also significantly reduced. Five of 10 patients completely discontinued maintenance oral corticosteroids. Ten patients with a baseline forced expiratory volume in 1 s of <60% predicted significantly improved from 49.2 ± 9.6% to 61.8 ± 17.6%, P < 0.05. Only two procedures required hospitalisation beyond the planned overnight admission. CONCLUSION: BT is a safe procedure which can achieve clinical improvement in those with uncontrolled symptoms and severe airflow obstruction.

Role of granulocyte-macrophage colony-stimulating factor in pulmonary fibrosis following pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized by accumulation of lipoproteinacious material in alveoli, with distinct features on high resolution computed tomography and biopsy. Its association with pulmonary fibrosis is infrequently encountered, and a clear understanding of the underlying pathogenesis is yet to be established. We report the case of a 48-year-old woman with known autoimmune PAP (aPAP) first diagnosed 20 years ago, who presented with worsening hypoxemia and radiological features consistent with pulmonary fibrosis, after many years of stable disease. We present a review of previously considered mechanisms of causation behind such changes, and in particular, postulate the role of granulocyte-macrophage colony-stimulating factor deficiency in pulmonary fibrosis seen in aPAP.