Diagnostic accuracy of lung ultrasound in diagnosis of ARDS and identification of focal or non-focal ARDS subphenotypes: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory condition with high mortality rates, accounting for 10% of all intensive care unit admissions. Lung ultrasound (LUS) as diagnostic tool for acute respiratory failure has garnered widespread recognition and was recently incorporated into the updated definitions of ARDS. This raised the hypothesis that LUS is a reliable method for diagnosing ARDS. OBJECTIVES: We aimed to establish the accuracy of LUS for ARDS diagnosis and classification of focal versus non-focal ARDS subphenotypes. METHODS: This systematic review and meta-analysis used a systematic search strategy, which was applied to PubMed, EMBASE and cochrane databases. Studies investigating the diagnostic accuracy of LUS compared to thoracic CT or chest radiography (CXR) in ARDS diagnosis or focal versus non-focal subphenotypes in adult patients were included. Quality of studies was evaluated using the QUADAS-2 tool. Statistical analyses were performed using "Mada" in Rstudio, version 4.0.3. Sensitivity and specificity with 95% confidence interval of each separate study were summarized in a Forest plot. RESULTS: The search resulted in 2648 unique records. After selection, 11 reports were included, involving 2075 patients and 598 ARDS cases (29%). Nine studies reported on ARDS diagnosis and two reported on focal versus non-focal ARDS subphenotypes classification. Meta-analysis showed a pooled sensitivity of 0.631 (95% CI 0.450-0.782) and pooled specificity of 0.942 (95% CI 0.856-0.978) of LUS for ARDS diagnosis. In two studies, LUS could accurately differentiate between focal versus non-focal ARDS subphenotypes. Insufficient data was available to perform a meta-analysis. CONCLUSION: This review confirms the hypothesis that LUS is a reliable method for diagnosing ARDS in adult patients. For the classification of focal or non-focal subphenotypes, LUS showed promising results, but more research is needed.

Clinical course of suspected familial and sporadic idiopathic pulmonary fibrosis: Data from the PROOF-Next registry.

BACKGROUND AND OBJECTIVE: Real-life data on suspected familial fibrosis, defined as the occurrence of the disease in a patient younger than 50 and/or having at least one relative affected by pulmonary fibrosis remain scarce. METHODS: The Belgian and Luxembourg IPF registry (PROOF-Next) is a multicentric prospective longitudinal and observational study set in Belgium and Luxembourg. We compared characteristics and clinical course of patients with suspected familial pulmonary fibrosis (FPF) and sporadic IPF. RESULTS: We included 618 patients in the analysis, of whom 76 (12%) fulfilled criteria for FPF. They were significantly younger than sIPF (median age (range) 65 (43-87), vs. 72 (51-98), p = 0.0001). Male gender proportion and smoking status did not differ between groups, but the number of pack-year among current and former smokers was lower in FPF (20 vs. 25, p = 0.02). Besides, 87% of FPF and 76% of sIPF were treated with antifibrotic (p = 0.047). Baseline pulmonary function tests were similar in both groups, as well as median time before progression and transplant-free survival. Finally, genetic testing, performed in a minority, led to the identification of 10 telomerase-related gene variants. CONCLUSION: Although younger and exposed to less tobacco, patients with FPF show an equally aggressive progression as observed in sporadic IPF patients. These results warrant early referral of FPF patients to expert centres for optimal management.

Thoracic Society of Australia and New Zealand clinical practice guideline on adult home oxygen therapy.

This Thoracic Society of Australia and New Zealand Guideline on the provision of home oxygen therapy in adults updates a previous Guideline from 2015. The Guideline is based upon a systematic review and meta-analysis of literature to September 2022 and the strength of recommendations is based on GRADE methodology. Long-term oxygen therapy (LTOT) is recommended for its mortality benefit for patients with COPD and other chronic respiratory diseases who have consistent evidence of significant hypoxaemia at rest (PaO2 ≤ 55 mm Hg or PaO2 ≤59 mm Hg in the presence of hypoxaemic sequalae) while in a stable state. Evidence does not support the use of LTOT for patients with COPD who have moderate hypoxaemia or isolated nocturnal hypoxaemia. In the absence of hypoxaemia, there is no evidence that oxygen provides greater palliation of breathlessness than air. Evidence does not support the use of supplemental oxygen therapy during pulmonary rehabilitation in those with COPD and exertional desaturation but normal resting arterial blood gases. Both positive and negative effects of LTOT have been described, including on quality of life. Education about how and when to use oxygen therapy in order to maximize its benefits, including the use of different delivery devices, expectations and limitations of therapy and information about hazards and risks associated with its use are key when embarking upon this treatment.

Exhaled aerosol increases with COVID-19 infection, age, and obesity.

COVID-19 transmits by droplets generated from surfaces of airway mucus during processes of respiration within hosts infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We studied respiratory droplet generation and exhalation in human and nonhuman primate subjects with and without COVID-19 infection to explore whether SARS-CoV-2 infection, and other changes in physiological state, translate into observable evolution of numbers and sizes of exhaled respiratory droplets in healthy and diseased subjects. In our observational cohort study of the exhaled breath particles of 194 healthy human subjects, and in our experimental infection study of eight nonhuman primates infected, by aerosol, with SARS-CoV-2, we found that exhaled aerosol particles vary between subjects by three orders of magnitude, with exhaled respiratory droplet number increasing with degree of COVID-19 infection and elevated BMI-years. We observed that 18% of human subjects (35) accounted for 80% of the exhaled bioaerosol of the group (194), reflecting a superspreader distribution of bioaerosol analogous to a classical 20:80 superspreader of infection distribution. These findings suggest that quantitative assessment and control of exhaled aerosol may be critical to slowing the airborne spread of COVID-19 in the absence of an effective and widely disseminated vaccine.

What is cystic fibrosis screen positive inconclusive diagnosis? And what is it not?

Since screening for cystic fibrosis (CF) was incorporated into the newborn screening program, the number of recognised variants in the CF transmembrane conductance regulator (CFTR) gene has significantly increased. This has led to the discovery of combinations of gene variants with an uncertain prognosis. One outcome is the designation of 'cystic fibrosis screen positive inconclusive diagnosis' (CFSPID). While the majority of these children are expected to be unaffected by their CFTR variants, a small proportion have been seen to develop symptoms or increasing sweat chloride levels over time, which may reflect dysfunction of the CFTR protein.As the number of children with CFSPID increases, paediatricians and those working in primary care are more likely to encounter them in their practice. It is important that professionals have an understanding of CFSPID: what it is and, importantly, what it is not (ie, they do not have CF). In this article, we hope to explore this using some example cases, illustrating the ways in which these children may present symptomatically and how to manage them.

Fifteen-minute consultation: Empowering children, young people and families through shared decision-making: a practical guide.

Shared decision-making (SDM) is a collaborative approach to healthcare decision-making that involves patients and healthcare professionals working together to make decisions that are informed by the best available medical evidence, as well as the patient's values, preferences and goals. The importance of SDM and the intricate interplay among parents, children and young people (CYP), and healthcare professionals are increasingly acknowledged as the crucial aspects of delivering high-quality paediatric care. While there is a substantial evidence base for SDM improving knowledge and reducing decisional conflict, the evidence for long-term measures such as improved health outcomes is limited and mainly inconclusive. To support healthcare teams in implementing SDM, the authors offer a practical guide to enhance decision-making processes and empower CYP and their families.

Delayed onset post-traumatic wound botulism.

A 41-year-old man developed rapidly progressive cranial neuropathies and muscle weakness followed by respiratory failure, requiring ventilation support. On examination, there was marked bilateral ptosis and ophthalmoplegia with bulbar, neck and proximal upper limb weakness. He had a recent open left humeral fracture that eventually required amputation. Despite immunoglobulin therapy, his progressive weakness continued. Multiple investigation results were inconclusive. Eventually, botulinum type A toxin was found positive, by which time the therapeutic window for antitoxin had passed. He continued on supportive management and was treated for concomitant infections and nosocomial illnesses. He was subsequently weaned from respiratory support and has made a good neurological recovery.

Neurosarcoidosis with chronic cough and Horner's syndrome.

A 62-year-old man attended ophthalmology for a simple ptosis repair. He had a chronic cough, a Horner's syndrome with post-gustatory hyperhidrosis. He was referred to the respiratory and neurology teams. MR scan of his head and neck found evidence of multifocal disease at the skull base and carotid canal, and further tests identified additional deposits in the hilar lymph nodes, heart and sacrum. A transbronchial biopsy confirmed the diagnosis of sarcoidosis. His symptoms and imaging responded well to corticosteroids, but he still undergoes regular imaging. We discuss the features of Horner's syndrome, and the autonomic associations of a chronic cough.

Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi.

BACKGROUND: In this phase 2 randomised placebo-controlled clinical trial in patients with COVID-19, we hypothesised that blocking mineralocorticoid receptors using a combination of dexamethasone to suppress cortisol secretion and spironolactone is safe and may reduce illness severity. METHODS: Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50 mg day 1, then 25 mg once daily for 21 days) or standard of care in a 2:1 ratio. Both groups received dexamethasone 6 mg daily for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category ≤ 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF). RESULTS: One hundred twenty patients with PCR confirmed COVID were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had significantly lower D-dimer levels on days 4 and 7 (day 7 mean D-dimer: SpiroDex 1.15 µg/mL, Dex 3.15 µg/mL, p = 0.0004) and aldosterone at day 7 (SpiroDex 6.8 ng/dL, Dex 14.52 ng/dL, p = 0.0075). There was no difference in VWF or angiotensin II levels between groups. For secondary outcomes, SpiroDex patients had a significantly greater number of oxygen free days and reached oxygen freedom sooner than the Dex group. Cough scores were no different during the acute illness, however the SpiroDex group had lower scores at day 28. There was no difference in corticosteroid levels between groups. There was no increase in adverse events in patients receiving SpiroDex. CONCLUSION: Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-dimer and aldosterone. Time to recovery was not significantly reduced. Phase 3 randomised controlled trials with spironolactone and dexamethasone should be considered. TRIAL REGISTRATION: The trial was registered on the Clinical Trials Registry of India TRI: CTRI/2021/03/031721, reference: REF/2021/03/041472. Registered on 04/03/2021.

Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.

PURPOSE: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

Unexplained Significant Central Sleep Apnea in Infants: Clinical Presentation and Outcomes.

OBJECTIVE: Unexplained significant central sleep apnea in term infants presents as central apneas with associated oxygen desaturations requiring respiratory support and monitoring for prolonged periods. However, there is a paucity of literature describing idiopathic central sleep apnea (ICSA) in term or near-term infants. Our aim was to describe the clinical manifestations, polysomnography data, interventions, and trajectory of ICSA in infants. DESIGN: This is a retrospective study of infants (gestational age ≥ 35 weeks) who presented with significant central apneas and were subsequently diagnosed with ICSA following polysomnography and clinical investigations between January 2011 and April 2021 at a tertiary care hospital in Canada. Polysomnography data, clinical investigations, and treatments were documented. RESULTS: Eighteen infants (male, 78%; median gestational age 38 weeks) with ICSA were included. Initial polysomnograms were completed at a median (interquartile range [IQR]) age of 1.2 (0.6-1.6) months (n = 18) and follow-up polysomnograms at 12.4 (10.6-14.0) months (n = 13). Compared to baseline diagnostic polysomnograms, at follow-up there was a significant reduction in the median (IQR) central apnea-hypopnea index (26.1 [18.2-52.9] versus 4.2 [2.6-7.2] events/hour; p = 0.001), desaturation index (30.9 [12.2-57.4] versus 3.9 [3.0-7.9] events/hour; p = 0.002), average transcutaneous carbon dioxide (41.9 [40.1-47.3 versus 39.4 [37.5-42.7] mmHg; p = 0.025), and improved nadir oxygen saturation (79.8 [69.1-83.0] versus 85.5 [83.2-87.8]%; p = 0.033), respectively. Prescribed treatments included supplemental oxygen (14/18, 78%), caffeine (5/18, 28%), and noninvasive ventilation (1/18, 6%). CONCLUSIONS: Infants with significant unexplained ICSA have a favorable clinical trajectory over time. Further research is needed to understand the etiology of this rare disorder.

Indwelling pleural catheters: evidence for and management.

The incidence of pleural disease is increasing, and pleural medicine is increasingly recognised as a subspecialty within respiratory medicine. This often requires additional training time. Once underresearched, the last decade has seen an explosion in evidence related to the management of pleural disease. One of the cornerstones of pleural effusion management is the insertion of an indwelling pleural catheter. This allows patient-centred outpatient management and now has a robust evidence base. This article summarises evidence as well serves as a practical guide to the management of any complications related to an indwelling pleural catheter that might present on an acute take.

Microalbuminuria on admission for acute exacerbation of COPD as a predictor of all-cause mortality and future exacerbations.

OBJECTIVES: Microalbuminuria (MAB) is a sensitive biomarker of cardiovascular risk that is directly associated with cardiovascular events and mortality. Recent studies have evaluated the presence of MAB in patients with stable chronic obstructive pulmonary disease (COPD) or hospitalised for acute exacerbation of COPD (AECOPD). METHODS: We evaluated 320 patients admitted for AECOPD in respiratory medicine departments of two tertiary hospitals. On admission, demographic, clinical and laboratory values and COPD severity were assessed. Patients were evaluated monthly for 1 year, recording new AECOPD and death from any cause. RESULTS: Patients with documented MAB (urinary albumin excretion of 30-300 mg/24 hours) on admission had worse lung function (forced expiratory volume in 1 s, %) (mean (SD) 34.2 (13.6)% vs 61.5 (16.7)%), higher modified Medical Research Council (3.6 (1.2) vs 2.1 (0.8)), lower 6 min walk test (171 (63) vs 366 (104)) and more hospitalisation days (9 (2.8) vs 4.7 (1.9)) (p < 0.001 for all comparisons). MAB was also correlated with Global Initiative for Chronic Obstructive Lung Disease 2020 COPD stages (p < 0.001). In multivariate regression analysis, MAB was a significant predictor of longer hospitalisation duration (OR 6.847, 95% CI 3.050 to 15.370, p < 0.0001). Twelve-month follow-up revealed that patients with MAB experienced more AECOPDs (4.6 (3.6) vs 2.2 (3.5), p < 0.0001) and deaths, n (%) (52 (36.6) vs 14 (7.8), p < 0.001). Kaplan-Meier survival curves demonstrated that patients with MAB presented with increased mortality, AECOPD and hospitalisation for AECOPD risk at 1 year (p < 0.001 for all comparisons). CONCLUSIONS: The presence of MAB on admission for AECOPD was associated with more severe COPD and prolonged hospitalisation, as well as with higher rates of AECOPD and mortality risk at 1-year follow-up.

Use of opioids for refractory dyspnoea in hospitalised patients with serious illness: a narrative review.

Refractory dyspnoea can be a challenging symptom to manage. Palliative care specialists are not always available for consultation, and while many clinicians may undergo training in palliative care, this education is not universal. Opioids are the most studied and prescribed pharmacological intervention for refractory dyspnoea; however, many clinicians hesitate to prescribe opioids due to regulatory concerns and fear of adverse effects. Current evidence suggests that rates of severe adverse effects, including respiratory depression and hypotension, are low when opioids are administered for refractory dyspnoea. Therefore, systemic, short-acting opioids are a recommended and safe option for the palliation of refractory dyspnoea in patients with serious illness, especially in a hospital setting that facilitates close observation. In this narrative review, we discuss the pathophysiology of dyspnoea; facilitate an evidence-based discussion on the concerns, considerations and complications associated with opioid administration for refractory dyspnoea; and describe one approach to managing refractory dyspnoea.

Electrocardiographic changes in a right-sided pneumothorax.

A pneumothorax is an extrapulmonary air accumulation within the pleural space between the lung and the chest wall. Symptoms usually reported include dyspnoea and chest pain. However, there are many life-threatening conditions with the same symptomology making early pneumothorax diagnosis challenging, such as acute coronary syndrome. Electrocardiogram (ECG) changes caused by left and right sided pneumathoraces have been reported, but awareness remains poor. This case describes a 51-year old male who presented with a right-sided pneumothorax, new ECG changes and elevated troponin. The case highlights the importance of recognising right-sided pneumothorax-associated ECG manifestations in patients presenting with acute chest symptoms.

Fifteen-minute consultation: A structured approach to children with parapneumonic effusion and empyema thoracis.

Parapneumonic effusion is defined as the accumulation of pleural fluid associated with lung infection/pneumonia. Parapneumonic effusions can be uncomplicated or complicated. They are caused by the spread of infection and inflammation to the pleural space, and can develop into empyema thoracis-frank pus in the pleural space. Chest radiograph and thoracic ultrasound are the key imaging modalities for the diagnosis of parapneumonic effusion. Management aims are reducing inflammation and bacteria in the pleural cavity, and enabling full lung expansion. Broad-spectrum intravenous antibiotics, with the addition of chest tube drainage and fibrinolytic therapy for larger collections, are the mainstays of management. This article provides a clear, evidence-based and structured approach to the assessment and management of parapneumonic effusion/empyema thoracis in children and young people.

Use of pulse oximetry as an investigative test for paediatric respiratory sleep disorders.

The article covers the following elements: practical and technological considerations for optimising data collection and output; reference ranges for oximetry parameters across the ages; things to consider when interpreting a pulse oximetry study (eg, sleep/wake times); the ability of pulse oximetry to predict obstructive sleep apnoea; using oximetry as a screening tool for sleep disordered breathing in children with Down syndrome; things to consider when setting up a home oximetry service; and a case of an infant being weaned from oxygen using pulse oximetry studies.

Ventilatory failure in chronic neuromuscular disease.

Patients with neuromuscular diseases (NMD) can present to the neurologist with symptoms and signs of respiratory failure, either acutely or as an insidious process in the outpatient setting. Since the advent of non-invasive ventilation, the outcomes of patients with ventilatory failure due to NMD have dramatically improved. However, the natural history of different NMDs requires a nuanced approach to respiratory investigation and management. Respiratory failure dictates the prognosis of many NMDs and timing the most appropriate investigation and referral to ventilation services is crucial in optimising care.

A reflection on Salbutamol overuse in one GP practice in Islington: a community action project at Imperial College London.

As 3rd-year medical students at Imperial College London, we investigated Salbutamol overuse in the community of Islington. We were inspired to carry out this project due to the high prevalence of Salbutamol overuse which became evident during our GP placement. This was part of our Community Action Project (CAP) which aims for students to investigate issues within their GP practice and patient population and create solutions to help overcome this, like a quality improvement project. This project focused on the local community around the GP practice. We spoke to 11 patients individually who were at high risk of severe asthma attacks, assessing their understanding of Salbutamol and their Salbutamol usage. Patients had varied responses, with some using their inhaler five times a day, to others using it very rarely. This project gave us newly found insight into the growing issue of Salbutamol overuse. Using the information gathered from these patient interviews, we produced an educational poster about Salbutamol inhaler usage.

The environmental impact of inhalers for asthma: A green challenge and a golden opportunity.

The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery of care. Most MDI use is in salbutamol relievers in patients with poorly controlled disease. The UK lags behind Europe in this regard, with greater reliance on salbutamol MDI and correspondingly greater greenhouse gas emissions, roughly treble that of our European neighbours. There has been a broad switch towards MDIs in asthma treatment in the UK over the last 20 years to reduce financial costs, such that the treatment for two-thirds of asthma patients in the UK is dominated by salbutamol MDI. Strategies that replace overuse of reliever MDIs with regimes emphasising inhaled corticosteroids have the potential to improve asthma control alongside significant reductions in greenhouse gas emissions. Real-world evidence shows that once-daily long-acting combination dry-powder inhalers (DPIs) can improve compliance and asthma control, and reduce the carbon footprint of care. Similarly, maintenance and reliever therapy (MART), which uses combination reliever and inhaled steroids in one device (usually a DPI), can simplify therapy, improve asthma control and reduce greenhouse gas emissions. Both treatment strategies are popular with patients, most of whom would be willing to change treatment to reduce their carbon footprint. By focussing on patients who are currently using high amounts of salbutamol MDI and prioritising inhaled steroids via DPIs, there are golden opportunities to make asthma care in the UK more effective, safer and greener.