Acute extreme hypocapnia and diabetic coma in an elderly patient after surgery: A case report.

Hyperglycemia and diabetic ketoacidosis are serious and life-threatening emergencies in diabetes patients. Early recognition of the symptoms of these disorders and their management are essential. Therapy is adequate rehydration, insulin treatment, electrolyte replacement, and handling of the underlying causative disease. Herein, we present an 83-year-old male with an extremely altered blood gas analysis after a surgical procedure of his left hand due to a phlegmon and describe the successful treatment through intensive care.

Respiratory viral testing for young febrile infants presenting to emergency care: a planned secondary analysis of the Febrile Infants Diagnostic assessment and Outcome (FIDO) prospective observational cohort study.

OBJECTIVE: To describe the association of respiratory viral test results and the risk of invasive bacterial infection (IBI) for febrile young infants presenting to emergency care. DESIGN: A planned secondary analysis within the Febrile Infants Diagnostic assessment and Outcome (FIDO) study, a prospective multicentre observational cohort study conducted across the UK and Ireland. SETTING: 35 paediatric emergency departments and assessment units across the UK and Ireland between 6 July 2022 and 31 August 2023. PATIENTS: Febrile infants aged 90 days and under presenting to emergency care. MAIN OUTCOME MEASURES: IBI (meningitis or bacteraemia) among febrile infants, undergoing respiratory viral testing for respiratory syncytial virus (RSV), influenza and SARS-CoV-2. RESULTS: 1395 out of 1821 participants underwent respiratory viral testing, of those tested 339 (24.5%) tested positive for at least one of, SARS-CoV-2, RSV or influenza. A total of 45 infants (3.2%) were diagnosed with IBI. Of these, IBI occurred in 40 out of 1056 (3.8%) participants with a negative viral test and 5 out of 339 (1.5%) occurred in participants with a positive viral respiratory test (p=0.034). Infants aged 29 days and older with a positive respiratory viral test had a significantly lower rate of IBI (0.7%) compared with those with a negative test (3.2%) (p=0.015). CONCLUSIONS: Young febrile infants with a positive respiratory viral test for SARS-CoV-2, RSV or influenza are at lower risk of IBI. Infants over 28 days of age with a positive viral test represent the lowest risk cohort. TRIAL REGISTRATION NUMBER: NCT05259683.

Sustainability assessment of a quality improvement initiative on the management of bronchiolitis.

BACKGROUND: A bronchiolitis integrated care pathway (BICP) achieved an 87% reduction in the use of medications in our regional health service (RHS) during the 2019-2020 season. AIM: This study aimed to assess the sustainability of the changes in bronchiolitis management over 3 years after implementation of the BICP. METHODS: A prospective observational study on rates of medications prescribing in children diagnosed with bronchiolitis in 135 primary care (PC) centres and eight hospital emergency departments (EDs) in the Basque Country, Spain, was conducted during the four bronchiolitis seasons between 2019 and 2023. Over this period, the deployment of BICP-related actions continued in our RHS. In addition, a strategy was designed to enhance the sustainability of the results. The main endpoint was the percentage of children prescribed salbutamol. RESULTS: Over the 2019-2020 to 2022-2023 epidemic waves, 12 966 infants were diagnosed with bronchiolitis in PC, and 6676 infants in EDs. Rates of salbutamol use over the four waves were 5.04%, 10.54%, 8.51% and 6.05%, respectively, in PC and 3.36%, 10.02%, 7.62% and 5.77% in EDs. Rates of concomitant administration of other medications in EDs over the four waves were 3.2%, 0.2%, 1.0% and 1.9% for epinephrine and 0.4%, 0.7%, 0.3% and 0.4% for corticosteroids, respectively. In PC, prescribing rates were 5.1% and 1.8%, 10.3% and 4.1% for antibiotics and 7.8% and 4.5%, 5.7% and 2.5% for corticosteroids, respectively. CONCLUSIONS: Reductions in the use of medications for bronchiolitis achieved in 2019 through the implementation of our integrated clinical pathway have been sustained over the three subsequent waves.

A case report of cardiopulmonary exercise testing and incentive spirometry-guided breathing pattern alteration for a severely tachypnoeic kyphoscoliotic patient undergoing major thoracic surgery for suspected lung malignancy.

A case report of a severely dyspnoeic kyphoscoliotic patient intended for an elective major thoracic surgery for suspected lung malignancy. With baseline near maximal breathing frequency and shallow breaths and poor lung mechanics, the first encountered anaesthetist considered this patient too high risk for lobectomy. This case illustrated the application of cardiopulmonary exercise testing to provide an objective assessment of the patient's functional capacity, ventilatory efficiency and delineation of modifiable respiratory components that guide the formulation of individualized prehabilitation programme. It also depicted the perioperative role of an off-label use of incentive spirometry in providing visual feedbacks and led to subsequent assessment breathing pattern alternation. Patient underwent the lung resection uneventfully and returned to normal lifestyle on postoperative day 4.

Real time monitoring of respiratory viral infections in cohort studies using a smartphone app.

Cohort studies investigating respiratory disease pathogenesis aim to pair mechanistic investigations with longitudinal virus detection but are limited by the burden of methods tracking illness over time. In this study, we explored the utility of a purpose-built AERIAL TempTracker smartphone app to assess real-time data collection and adherence monitoring and overall burden to participants, while identifying symptomatic respiratory illnesses in two birth cohort studies. We observed strong adherence with daily app usage over the six-month study period, with positive feedback from participant families. A total of 648 symptomatic respiratory illness events were identified with significant variability between individuals in the frequency, duration, and virus detected. Collectively, our data show that a smartphone app provides a reliable method to capture the longitudinal virus data in cohort studies which facilitates the understanding of early life infections in chronic respiratory disease development.

Fifteen-minute consultation: considering greener asthma treatments for children and young people.

Inhalers are the mainstay of asthma treatment, but are responsible for a disproportionately high level of carbon emissions compared with other aspects of healthcare. There is a growing interest among CYP in discussing the environmental impact of their treatment with healthcare staff. In this article, we outline an individualised approach to modifying asthma treatment to be more sustainable. We explore options including prescribing dry powder inhalers over pressurised metered dose inhalers, choosing inhaler devices with lower carbon footprints, improving disposal and recycling of inhalers, and optimising basic asthma care through routine reviews, prescription management and during exacerbations.

Use of CFTR modulators in pregnancy: new information for neonatal, paediatrics and midwifery teams.

Cystic fibrosis (CF) is common, multisystem, life-limiting genetic condition, predominantly in the Caucasian population. There have been recent advances in the management of CF, in particular in the last 5 years following approval of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators by the National Health Service (NHS) for use in people with CF (pwCF).Traditionally, almost 40% of female patients with CF (fwCF) and over 95% of male patients with CF (mwCF) have issues with subfertility or infertility. CFTR modulators have transformed the lives of pwCF who have the specific genetic variants that respond to the treatment.Women taking CFTR modulators, particularly highly effective CFTR modulators (elexacaftor, tezacaftor and ivacaftor), have shown resolution of infertility and successful pregnancies without fertility treatment. At present male patients taking CFTR modulators have not shown improvement in infertility. Unplanned pregnancies are on the increase in fwCF. fwCF have had significantly improved general health when taking CFTR modulators. Subsequently many fwCF now become pregnant and choose to continue their pregnancies to term, with positive outcomes.Clinical and biochemical status of the newborn babies with CF, who are born to fwCF on CFTR modulators, can be very different when compared with the other babies with CF who are unexposed to CFTR modulators in utero.New opportunities bring new challenges. This review highlights how infants exposed to CFTR modulators in utero can be affected, and suggests how they should be monitored.

Management of a rare case of lymphangioleiomyomatosis complicated by recurrent pneumothorax.

A female of reproductive age presents to the emergency department with progressive dyspnoea due to pneumothorax. She has a history of lymphangioleiomyomatosis (LAM) diagnosed by lung biopsy 15 years ago following incidental finding of pneumothorax. Despite various procedural and medicinal treatments, she continued to have recurrent pneumothorax, with three hospital admissions over the preceding 3 months. LAM is a rare cystic lung disease affecting the lymphatic system, which most commonly affects women of childbearing age. It can be diagnosed via imaging or tissue biopsy (gold standard). Treatment can be difficult, and it often requires highly specialised care by pulmonologists and often confers significant limitations to patients' independence and quality of life. Family physicians are often part of multidisciplinary team to provide care to patients with rare chronic conditions.

High burden of respiratory allergy in children warrants early identification and treatment with allergen immunotherapy.

Respiratory allergy often begins in childhood and most commonly manifests as allergic rhinitis (upper airways) and/or asthma (lower airways).) Children with upper respiratory allergy often suffer from coexisting asthma, and other comorbidities ranging from gastrointestinal disorders to emotional/mental health disorders. Consequently, the disease burden is considerable and profoundly impacts a child's daily life. Early identification and appropriate management are important to reduce disease burden, lower the risk of disease progression and additional comorbidities, and protect the child's future well-being. A window of opportunity for halting disease progression may open in the early stages of allergic disease and underlines the importance of early diagnosis and treatment of children at risk. This review offers advice on identifying children with a high disease burden who would benefit from early intervention. Allergen immunotherapy (AIT) modifies the cause of respiratory allergy and prevents disease progression. In clinical practice, AIT could be considered as an early treatment for eligible children, to achieve long-term symptom control and disease modification.

Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19.

We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular adhesion molecule-1 (sICAM), and soluble vascular cell adhesion molecule-1 with risk of COVID-19 outcomes. sICAM was positively associated with atopic asthma risk, whereas tumor necrosis factor-alfa showed an inverse association. A positive association was shown between interleukin-18 and COPD risk (replicated in observational analysis), whereas an inverse association was shown for interleukin-1 receptor antagonist (IL-1ra). IL-1ra and monocyte chemotactic protein-3 were positively associated with lung function indices, whereas inverse associations were shown for MCSF and interleukin-18 (replicated in observational analysis). Our results point to these cytokines as potential pharmacological targets for respiratory traits.

Lung abscess following a foreign body extraction.

Lung abscesses are uncommon in the paediatric population, often manifesting with cough, shortness of breath, chest pain and fever. A high index of suspicion is imperative to prevent delays in treatment. This is a case report of a previously healthy child in early childhood with a 5-month history of recurrent left upper lobe (LUL) pneumonia. A foreign body was identified in the LUL and removed via flexible bronchoscopy. Following the foreign body removal, the patient developed a 9 cm lung abscess. A high index of suspicion for a lung abscess post-foreign body removal is important for early diagnosis and ensuring appropriate antibiotic coverage in patients with persistent fever. Intravenous antibiotics are essential in the management of lung abscesses. Consideration should be given to percutaneous drainage in situations where there is minimal improvement after 72 hours of suitable antimicrobial therapy or when the abscess exceeds 6 cm in size.

Differences in pulmonary function measured by oscillometry between horses with mild-moderate equine asthma and healthy controls.

BACKGROUND: The diagnosis of mild-moderate equine asthma (MEA) can be confirmed by airway endoscopy, bronchoalveolar lavage fluid (BALf) cytology, and lung function evaluation by indirect pleural pressure measurement. Oscillometry is a promising pulmonary function test method, but its ability to detect subclinical airway obstruction has been questioned. OBJECTIVES: To evaluate the differences in lung function measured by oscillometry between healthy and MEA-affected horses. STUDY DESIGN: Prospective case-control clinical study. METHODS: Thirty-seven horses were divided into healthy and MEA groups, based on history and clinical score; the diagnosis of MEA was confirmed by airway endoscopy and BALf cytology. Horses underwent oscillometry at frequencies ranging from 2 to 6 Hz. Obtained parameters included whole-breath, inspiratory, expiratory, and the difference between inspiratory and expiratory resistance (Rrs) and reactance (Xrs). Differences between oscillometry parameters at different frequencies were evaluated within and between groups by repeated-measures two-way ANOVA and post hoc tests with Bonferroni correction. Frequency dependence was compared between groups by t test. For significant parameters, a receiver operating characteristics curve was designed, cut-off values were identified and their sensitivity and specificity were calculated. Statistical significance was set at p < 0.05. RESULTS: No significant differences in Xrs and Rrs were observed between groups. The frequency dependence of whole-breath and inspiratory Xrs significantly differed between healthy (respectively, -0.03 ± 0.02 and -0.05 ± 0.02 cmH2O/L/s) and MEA (-0.1 ± 0.03 and -0.2 ± 0.02 cmH2O/L/s) groups (p < 0.05 and p < 0.01). For inspiratory Xrs frequency dependence, a cut-off value of -0.06 cmH2O/L/s was identified, with 86.4% (95% CI: 66.7%-95.3%) sensitivity and 66.7% (95% CI: 41.7%-84.8%) specificity. MAIN LIMITATIONS: Sample size, no BALf cytology in some healthy horses. CONCLUSIONS: Oscillometry can represent a useful non-invasive tool for the diagnosis of MEA. Specifically, the evaluation of the frequency dependence of Xrs may be of special interest.

Phase 0 trials/ Intra-Target-Microdosing (ITM) and the lung: a review.

The COVID-19 pandemic has highlighted the importance of efficient drug discovery in respiratory disease. The traditional set up of clinical trials is expensive and allows for significant attrition of new drugs, many of which undergo extensive safety testing before being abandoned for lack of efficacy. Phase 0 trials, named as they sit between pre-clinical research and phase I, allow for the testing of sub-clinical microdoses in humans to gather early pharmacokinetic (PK), pharmacodynamic (PD) and mechanistic data, before deciding on which drugs to advance further. This early data can improve the efficiency and cost effectiveness of drug development and reduce the extent of animal testing. Phase 0 trials traditionally have utilised sub-therapeutic microdoses of compounds administered intravenously with readouts focusing on PK - measured using highly sensitive methods such as accelerator mass spectrometry (AMS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) of peripheral blood, as well as whole-body positron emission tomography (PET). Mathematical models allow for extrapolation of this PK data to support the further testing of larger, systemically effective doses. However, this extrapolation method is limited at providing robust PD or target engagement/ mode of action data. Using an Intra-Target Microdosing (ITM) approach, a small compartment of the body (about 1% or less) is exposed to potentially clinically active local concentrations. This allows for the collection of PD data, evidence of target cell engagement, as well as the opportunity to extrapolate systemic PK and PD data. This approach has the potential within the pulmonary system for the study and rapid and cost-effective development of new and repurposed drugs.

Cavitary lung lesions caused by Pneumocystis jirovecii in a patient with myelofibrosis on ruxolitinib.

We report a rare case of a patient with Janus kinase 2-positive myelofibrosis on ruxolitinib, presenting with indolent pneumonia and cavitary lung lesions. Initial transthoracic biopsy was non-specific, but thoracoscopic biopsy revealed necrotising granulomatous disease caused by Pneumocystis jirovecii pneumonia (PJP). The patient, initially treated with trimethoprim-sulfamethoxazole, was switched to atovaquone due to gastrointestinal intolerance. Given the patient's immunosuppression and extensive cavitary lesions, an extended course of atovaquone was administered, guided by serial imaging, resulting in clinical and radiological improvement. Unfortunately, the patient later passed away from a severe SARS-CoV-2 infection before complete radiographic resolution was observed. This case highlights the importance of recognising atypical PJP presentations causing granulomatous disease in immunosuppressed patients. While rare, documenting such cases may improve diagnosis using less invasive methods and help determine optimal treatment durations for resolution of these atypical infections.

Mediastinal lymphadenopathy due to VEXAS syndrome.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a rare disease first reported in 2020, most commonly seen in men aged 56-75 years old. Common clinical features include skin lesions (83.5%), fever (63.6%), relapsing chondritis (36.4%), venous thrombosis (34.7%) and lymph node enlargement (33.9%). The patient is a man in his 40s who presented with testicular and lower extremity pain, followed by a rash and bicytopenia. He was initiated on corticosteroids and sulfasalazine. He was found to have mediastinal lymphadenopathy and underwent an endobronchial ultrasound and transbronchial needle aspiration followed by a video-assisted thoracic surgery biopsy which were unrevealing. Eventually, an ubiquitin-like modifier activating enzyme (UBA-1) gene analysis was performed that was consistent with VEXAS syndrome. Patients with VEXAS syndrome usually present with a red or violaceous rash and dyspnoea. Laboratory abnormalities include anaemia, elevated mean corpuscular volume, thrombocytopenia and elevated inflammatory markers. Diagnosis is based on the genetic mutation and associated symptoms. The treatment includes steroids and Janus kinase (JAK) inhibitors, specifically ruxolitinib.