Nalbuphine Tablets for Cough in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: There are no approved therapies for cough in patients with idiopathic pulmonary fibrosis (IPF). In this small crossover trial we administered nalbuphine extended-release tablets (NAL ER) as a potential cough therapy for such patients. METHODS: This randomized, double-blind, placebo-controlled, crossover trial involved two 22-day treatment periods (NAL ER→placebo and placebo→NAL ER) separated by a 2-week washout period. NAL ER was started at a dose of 27 mg once daily and was titrated up to 162 mg twice daily at day 16. The primary end point was percent change from baseline in hourly daytime objective cough frequency as measured by an electronic cough monitor. The daytime period was defined as the patient-reported time of awakening and bedtime. Secondary end points included change in objective 24-hour cough frequency, changes in cough frequency, cough severity, and breathlessness, per patient-reported outcomes. RESULTS: A total of 41 patients were randomly assigned and received one or more doses of study medication. There was a 75.1% reduction in daytime objective cough frequency during the NAL ER treatment period versus the placebo treatment period of 22.6%, a 52.5 percentage point placebo-adjusted decrease from baseline (P<0.001) at day 21. There was a 76.1% (95% confidence interval, 83.1 to 69.1) decrease in the 24-hour objective cough frequency with NAL ER, versus a 25.3% (43.9 to 6.7) decrease with placebo, a 50.8 percentage point placebo-adjusted change. Nausea, fatigue, constipation, and dizziness were more common with NAL ER than with placebo. CONCLUSIONS: In this short-term crossover trial, NAL ER reduced cough in individuals with IPF. Larger and longer trials are needed to assess the impact on cough versus drug adverse effects. (Funded by Trevi Therapeutics; ClinicalTrials.gov number, NCT04030026.)

Pulmonary Sequelae at 4 Months After COVID-19 Infection: A Single-Centre Experience of a COVID Follow-Up Service.

INTRODUCTION: At the end of the first year of the COVID-19 pandemic, more than 78 million known survivors were recorded. The long-term pulmonary sequelae of COVID-19 remain unknown. METHODS: We performed a retrospective analysis of a post-COVID follow-up service to estimate the burden of persistent pulmonary morbidity in hospitalised COVID survivors. RESULTS: A total of 221 patients were followed-up: 44 intensive care unit (ICU) and 177 ward patients. Further investigations were planned as per British Thoracic Society Guidelines: For all ICU patients (n = 44) and for 38 of 177 (21%) ward-based patients who had persistent symptoms and/or persistent radiographic changes on CXR at their initial 8-week follow-up visit. In the ward-based cohort, statistically significant associations with persistent symptoms were being an ex- or current smoker, having pre-existing diabetes, and having a longer length of stay. In patients requiring further investigations, pulmonary function tests (PFTs; n = 67) at an average of 15 weeks post-discharge showed abnormalities in at least one PFT parameter in 79% (equating to 24% of the entire cohort). The most common abnormality was an abnormal diffusion capacity of carbon monoxide (TLCO), highest in the ICU cohort (64% ICU vs. 38% non-ICU). TLCO correlated negatively with length of stay and with maximum inspired FiO2 in the patient group as a whole. In ICU patients, TLCO correlated negatively with maximum inspired positive airway pressure. Computed tomography scans (n = 72) at an average of 18 weeks post-discharge showed evidence of persistent ground glass opacities in 44% and fibrosis in 21% (equating to 7% of the entire cohort). CONCLUSION: Our data add to the growing evidence that there will be pulmonary sequelae in a proportion of COVID survivors, providing some insight into what may become a significant chronic global health problem.

The extended utility of antifibrotic therapy in progressive fibrosing interstitial lung disease.

INTRODUCTION: The approval of two antifibrotic treatment agents for delaying disease progression in idiopathic pulmonary fibrosis (IPF), has prompted researchers to look at expanding the role of antifibrotic therapy to other fibrosing interstitial lung disease (ILD). Similarities in the pathological mechanisms that lead to the development of IPF have been implicated in other progressive fibrosing ILD (PF-ILD) such as chronic hypersensitivity pneumonitis, connective tissues disease associated ILD, sarcoidosis, occupational ILD and idiopathic non-specific interstitial pneumonia (iNSIP). This has prompted the rationale to use antifibrotic therapy to target similar molecular pathways in these diseases. AREAS COVERED: This review will summarise the available evidence from randomised controlled trials that have evaluated the use of antifibrotic therapy in PF-ILD outside the realm of IPF. EXPERT OPINION: There is promising data for antifibrotic therapy as a therapeutic option for non IPF PF-ILD. The new therapy option does provide some challenges that need to be addressed such as timing of initiation of therapy, clarifying the strategy for overlap or combination with existing immunosuppressive therapies and potential drug interactions. There is an unmet need to determine accurate predictors of disease progression to allow early intervention for the preservation of lung function and mortality reduction.

Training opportunities in thoracic ultrasound for respiratory trainees: are current guidelines practical?

Introduction: Respiratory trainees in the UK face challenges in meeting current Royal College of Radiologists (RCR) Level 1 training requirements for thoracic ultrasound (TUS) competence, specified as attending 'at least one session per week over a period of no less than 3 months, with approximately five scans per session performed by the trainee (under supervision of an experienced practitioner)'. We aimed to clarify where TUS training opportunities currently exist for respiratory registrars. Methods: Data were collected (over a 4-week period) to clarify the number of scans (and therefore volume of training opportunities) within radiology departments and respiratory services in hospitals in the South West, North West deaneries and Oxford. Results: 14 hospitals (including three tertiary pleural centres) provided data. Of 964 scans, 793 (82.3%) were conducted by respiratory teams who performed a mean of 17.7 scans per week, versus 3.1 TUS/week in radiology departments. There was no radiology session in any hospital with ≥5 TUS performed, whereas 8/14 (86%) of respiratory departments conducted such sessions. Almost half (6/14) of radiology departments conducted no TUS scans in the period surveyed. Conclusions: The currently recommended exposure of regularly attending a list or session to undertake five TUS is not achievable in radiology departments. The greatest volume of training opportunities exists within respiratory departments in a variety of scheduled and unscheduled settings. Revision of the competency framework in TUS, and where this is delivered, is required.

[Nutrition in preschool children from Baile-Herculane]. / Alimentatia la copiii prescolari din Baile Herculane.

In the effected study we investigated the feeding quality in Baile-Herculane, during the period 2003-2004. The study was realised in two samples consisted in 659 preschool children (55% girls and 45% boys) and 359 children (65% girls and 35% boys) respectively, homogenous and statistical representative. The method consisted in feeding investigation using based on food lists consulting, effected 2 times in a year, in the winter season (November) and in the spring season (April). The inquiry period was 10 days consequently, in each season. We had established the nutritive value of feeding portions in two months (November and April), counted the average of the nutritive ration for the both investigated periods and compared them with nutritional necessity established for the same age group. We investigated the menu structure and diversity. In the first period of feeding investigation (November 2000) we established a decreased intake of foods which determine a small intake of calories, proteins, minerals and vitamins under the nutritional necessities. In April the nutritive value of the consumed food was less than in November. The decreased consumption of milk, cheese, eggs, vegetables and fruits determined a less intake of calories, fats, minerals and vitamins than nutritional necessities. The increased intake of bread, cereals and meat caused increased values of carbohydrates, vitamin B1 and iron. The menu was divided in two meals and a snack (breakfast - 15%, snack - 15%, lunch 50%). The menu variation and courses' succession were in line with the hygienic-sanitation rules.