One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial.

Rationale: The combination of noradrenergic and antimuscarinic agents has recently been shown to improve upper-airway function and reduce obstructive sleep apnea (OSA) severity in short-term (⩽1 wk) proof-of-concept studies. Objectives: To determine the safety, tolerability, and potential efficacy of longer term use of different doses of the noradrenergic agent atomoxetine combined with the antimuscarinic oxybutynin (ato-oxy). Methods: Thirty-nine people with predominantly severe OSA received 80/5 mg ato-oxy, 40/5 mg ato-oxy, 40/2.5 mg ato-oxy, or placebo nightly for 30 days in a double-blind, randomized, parallel design. Participants completed three in-laboratory sleep studies (baseline, Night 1, and Night 30) to assess efficacy. Vital signs and objective measures of alertness and memory were assessed. In men, potential effects on prostate function were assessed using the International Prostate Symptom Score at baseline and Night 30. Potential adverse events were assessed during in-laboratory visits and via weekly phone calls. Results: Side effects were generally mild and consistent with known side-effect profiles of each individual drug (i.e., dose-dependent increases in dry mouth with oxybutynin). Heart rate increased by Night 30 in two active drug arms (mean ± standard deviation 8 ± 10 beats/min [P = 0.01] with 80/5 mg and 9 ± 14 beats/min [P = 0.02] with 40/2.5 mg vs. placebo). No clinically relevant changes in blood pressure, International Prostate Symptom Score, and measures of alertness and memory were observed between conditions. Apnea-hypopnea index (AHI) with 4% oxygen desaturation and hypoxic burden decreased by ∼50% with 80/5 mg ato-oxy from baseline but not versus placebo (e.g., AHI with 3% oxygen desaturation and AHI with 4% oxygen desaturation difference at Night 30 was -8.2 [95% confidence interval, -22.5 to 6.2] and -8.5 [95% confidence interval, -18.3 to 1.3] events/h, respectively). Conclusions: One month of nightly noradrenergic and antimuscarinic combination therapy was generally well tolerated, with a side-effect profile consistent with each agent alone, and was associated with an ∼50% reduction from baseline in a key OSA severity metric, the hypoxic burden with the highest dose combination. These findings highlight the potential to target noradrenergic and antimuscarinic mechanisms for OSA pharmacotherapy development. Clinical trial registered with www.anzctr.org.au (ACTRN 12619001153101).

Contemporary Concise Review 2020: Sleep.

Obstructive sleep apnoea (OSA) now affects one-seventh of the world's population. Treatment of even mild OSA can improve daytime sleepiness and quality of life. Recent modifications to uvulopalatopharyngoplasty may make it a more widely applicable treatment option in selected patients with OSA. Diet and exercise have effects on sleep apnoea severity independent of weight loss. Insomnia has become increasingly common during the coronavirus disease 2019 (COVID-19) pandemic.

Timing it right: the challenge of recipient selection for lung transplantation.

Selection criteria for the referral and potential listing of patients for lung transplantation (LTx) have changed considerably over the last three decades but one key maxim prevails, the ultimate focus is to increase longevity and quality of life by careful utilization of a rare and precious resource, the donor organs. In this article, we review how the changes have developed and the outcomes of those changes, highlighting the impact of the lung allocation score (LAS) system. Major diseases, including interstitial lung disease (ILD), chronic obstructive pulmonary disease and pulmonary hypertension are considered in detail as well as the concept of retransplantation where appropriate. Results from bridging to LTx using extracorporeal membrane oxygenation (ECMO) are discussed and other potential contraindications evaluated such as advanced age, frailty and resistant infections. Given the multiplicity of risk factors it is a credit to those working in the field that such excellent and improving results are obtained with an ongoing dedication to achieving best practice.

Antibiotic instillation for a chronic lung abscess.

INTRODUCTION: Antibiotic treatment of lung abscesses fails in 10-20% of cases and require surgery, however, some are unsuitable for resection. Alternative options carry significant morbidity. CASE REPORT: A 47 year old man with inoperable non-small cell lung cancer developed a lung abscess following definitive radiotherapy. Initial antibiotic therapy was successful, however four years later his symptoms recurred. Despite multiple courses his symptoms recurred despite long-term antibiotics. Immediately following a diagnostic aspiration, ceftriaxone and metronidazole were instilled into the abscess with subsequent clinical and radiological resolution. DISCUSSION: Lung abscesses are an uncommon complication of radiotherapy. Antibiotic therapy can fail for a number of reasons. Although instillation of antibiotics has not been described in the management of lung abscesses, the direct application of antifungals for aspergillomas is well documented and case series report success in other abscess sites. CONCLUSION: Direct antibiotic instillation following lung abscess aspiration adds minimal risk and is potentially curative.