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1.
iScience ; 27(10): 110704, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39319267

RESUMEN

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.

2.
Respir Med ; : 107812, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39326679

RESUMEN

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.

3.
Arch Dis Child ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251332

RESUMEN

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.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39288989

RESUMEN

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.

5.
Respirology ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240461
6.
Artículo en Inglés | MEDLINE | ID: mdl-39304332

RESUMEN

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.

7.
SAGE Open Med Case Rep ; 12: 2050313X241275384, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39290560

RESUMEN

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.

8.
BMJ Case Rep ; 17(9)2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39304215

RESUMEN

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.


Asunto(s)
Linfangioleiomiomatosis , Neumotórax , Recurrencia , Humanos , Linfangioleiomiomatosis/complicaciones , Linfangioleiomiomatosis/diagnóstico , Neumotórax/etiología , Neumotórax/terapia , Femenino , Neoplasias Pulmonares/complicaciones , Adulto , Tomografía Computarizada por Rayos X , Disnea/etiología
9.
BMJ Case Rep ; 17(8)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39214573

RESUMEN

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.


Asunto(s)
Nitrilos , Pneumocystis carinii , Neumonía por Pneumocystis , Mielofibrosis Primaria , Pirazoles , Pirimidinas , Humanos , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/complicaciones , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/diagnóstico , Pirimidinas/uso terapéutico , Pirazoles/uso terapéutico , Pneumocystis carinii/aislamiento & purificación , Masculino , Resultado Fatal , COVID-19/complicaciones , Atovacuona/uso terapéutico , Huésped Inmunocomprometido , Anciano , SARS-CoV-2
10.
BMJ Case Rep ; 17(8)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39122375

RESUMEN

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.


Asunto(s)
Linfadenopatía , Humanos , Masculino , Linfadenopatía/etiología , Adulto , Enzimas Activadoras de Ubiquitina/genética , Enfermedades del Mediastino/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/genética , Diagnóstico Diferencial , Síndrome , Nitrilos , Pirazoles , Pirimidinas
12.
BMJ Case Rep ; 17(8)2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134337

RESUMEN

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.


Asunto(s)
Antibacterianos , Broncoscopía , Cuerpos Extraños , Absceso Pulmonar , Humanos , Absceso Pulmonar/etiología , Cuerpos Extraños/complicaciones , Cuerpos Extraños/cirugía , Antibacterianos/uso terapéutico , Masculino , Drenaje/métodos , Preescolar , Tomografía Computarizada por Rayos X
13.
Equine Vet J ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134475

RESUMEN

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.

16.
BMJ Open ; 14(8): e086394, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153779

RESUMEN

INTRODUCTION: Chronic respiratory morbidity from bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth and has consequences for later respiratory, cardiovascular and neurodevelopmental outcomes. The early phases of respiratory illness are characterised by rapid consumption of endogenous surfactant and slow replenishment. Exogenous surfactant is routinely administered to infants born before 28 weeks of gestation as prophylaxis. Endogenous surfactant includes four proteins, known as surfactant proteins (SPs) A, B, C and D. Current bovine-derived and porcine-derived surfactant preparations only contain SPs B and C. SP-D has a key role in lung immune homeostasis as part of the innate immune system. Laboratory studies using recombinant SP-D have demonstrated reduced inflammation, which may be a pathway to reducing the associated morbidity from BPD. RESPONSE uses a recombinant fragment of human SP D (rfhSP-D), in a phase I safety and dose-escalation trial as the first stage in determining its effect in humans. METHODS AND ANALYSIS: This is a single-centre, dose-escalation, phase I safety study aiming to recruit 24 infants born before 30 weeks gestation with respiratory distress syndrome. In addition to routine surfactant replacement therapy, participants will receive three doses of rfhSP-D via endotracheal route at either 1 mg/kg, 2 mg/kg or 4 mg/kg. The study uses a Bayesian continual reassessment method to make dose escalation decisions. Dose-limiting events (DLE) in this trial will be graded according to the published Neonatal Adverse Event Severity Score. The primary outcome of this study is to evaluate the safety profile of rfhSP-D across each dose level based on the profile of DLE to establish the recommended phase 2 dose (RP2D) of rfhSP-D. ETHICS AND DISSEMINATION: The RESPONSE study has received ethical approval from London-Brent NHS Research Health Authority ethics committee. Results from the study will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBERS: ISRCTN17083028, NCT05898633. PROTOCOL VERSION: RESPONSE Protocol V.4.0 24th July 2024.


Asunto(s)
Proteína D Asociada a Surfactante Pulmonar , Proteínas Recombinantes , Síndrome de Dificultad Respiratoria del Recién Nacido , Humanos , Recién Nacido , Síndrome de Dificultad Respiratoria del Recién Nacido/prevención & control , Proteínas Recombinantes/administración & dosificación , Recien Nacido Prematuro , Displasia Broncopulmonar/prevención & control , Ensayos Clínicos Fase I como Asunto , Femenino , Masculino
17.
BMJ Case Rep ; 17(8)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39159986

RESUMEN

A woman in her early 30s presented to her primary care physician's office with hoarseness, joint pain and facial swelling. The objective evaluation revealed elevated inflammatory markers and angiotensin-1-converting enzyme, a chest radiograph with bilateral hilar prominence and a maxillofacial CT scan with diffuse inflammation in the upper airway. Otolaryngology evaluation revealed exophytic lesions diffusely within the nasal cavity, base of tongue, supraglottis, glottis and trachea. A biopsy confirmed the diagnosis of sarcoidosis. She was treated with corticosteroids with improvement in upper and lower airway symptoms. She continued to experience other extrapulmonary manifestations of sarcoidosis requiring alternative immunosuppressant therapy. At 30 months from symptom onset, her disease was noted to be in remission.


Asunto(s)
Enfermedades de la Laringe , Sarcoidosis , Enfermedades de la Tráquea , Humanos , Femenino , Sarcoidosis/diagnóstico , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/patología , Enfermedades de la Laringe/tratamiento farmacológico , Enfermedades de la Laringe/diagnóstico , Enfermedades de la Laringe/patología , Enfermedades de la Laringe/diagnóstico por imagen , Adulto , Enfermedades de la Tráquea/diagnóstico , Enfermedades de la Tráquea/diagnóstico por imagen , Enfermedades de la Tráquea/patología , Tomografía Computarizada por Rayos X , Tráquea/patología , Tráquea/diagnóstico por imagen
18.
Artículo en Inglés | MEDLINE | ID: mdl-39160076

RESUMEN

OBJECTIVE: To determine the accuracy of pre-extubation lung ultrasound (LUS) to predict reintubation in preterm infants born <32 weeks' gestation. DESIGN: Prospective diagnostic accuracy study. SETTING: Two neonatal intensive care units. METHODS: Anterior and lateral LUS was performed pre-extubation. The primary outcome was the accuracy of LUS scores (range 0-24) to predict reintubation within 72 hours. Secondary outcomes were accuracy in predicting (1) reintubation within 7 days, (2) reintubation stratified by postnatal age and (3) accuracy of lateral imaging only (range 0-12). Pre-specified subgroup analyses were performed in extremely preterm infants born <28 weeks' gestation. Cut-off scores, sensitivities and specificities were calculated using receiver operating characteristic analysis and reported as area under the curves (AUCs). RESULTS: One hundred preterm infants with a mean (SD) gestational age of 27.4 (2.2) weeks and birth weight of 1059 (354) g were studied. Thirteen were subsequently reintubated. The AUC (95% CI) of the pre-extubation LUS score for predicting reintubation was 0.63 (0.45-0.80). Accuracy was greater in extremely preterm infants: AUC 0.70 (0.52-0.87) and excellent in infants who were <72 hours of age at the time of extubation: AUC 0.90 (0.77-1.00). Accuracy was poor in infants who were >7 days of age. Lateral imaging alone demonstrated similar accuracy to scanning anterior and lateral regions. CONCLUSIONS: In contrast to previous studies, LUS was not a strong predictor of reintubation in preterm infants. Accuracy is increased in extremely preterm infants. Future research should focus on infants at highest risk of extubation failure and consider simpler imaging protocols. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12621001356853.

19.
BMC Pulm Med ; 24(1): 425, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210357

RESUMEN

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.


Asunto(s)
Pulmón , Humanos , Pulmón/diagnóstico por imagen , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Desarrollo de Medicamentos/métodos , COVID-19 , Ensayos Clínicos como Asunto
20.
Arch Dis Child ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39214692
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