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Journal articleSousa-Pinto B, Louis G, Vieira RJ, et al., 2024,
Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study
, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 14 -
Journal articleMortaz E, Folkerts G, Varahram M, et al., 2024,
Galacto-oligosaccharides and toll like receptor ligands 9 potentiates phagocytosis of bacteria by neutrophils from patients with non-small cells lung cancer (NSCLC)
, Microbial Biotechnology, ISSN: 1751-7907 -
Journal articleMacdonald H, Hardy H, Rahimi K, et al., 2024,
Protecting BMJ journals' content from tobacco industry influence
, BMJ: British Medical Journal, Vol: 385, Pages: q1169-q1169, ISSN: 0959-535X -
Journal articleGhanei M, Philip KEJ, Moghadam MRS, et al., 2024,
Pulmonary rehabilitation in Iranian outpatients with mustard gas lung disease: a randomised controlled trial
, BMJ Open, Vol: 14, ISSN: 2044-6055Objective People with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition.Design An assessor-blind, two-armed, parallel-design randomised controlled clinical trial.Setting Secondary care clinics in Iran.Participants 60 men with breathlessness due to respiratory disease caused by documented mustard gas exposure, mean (SD) age 52.7 (4.36) years, MRC dyspnoea score 3.5 (0.7), St. George’s Respiratory Questionnaire (SGRQ) 72.3 (15.2).Interventions Participants were allocated either to a 6-week course of thrice-weekly PR (n=31) or to usual care (n=29), with 6-week data for 28 and 26, respectively.Outcome measures Primary endpoint was change in cycle endurance time at 70% baseline exercise capacity at 6 weeks. Secondary endpoints included 6 min walk distance, quadriceps strength and bulk, body composition and health status. For logistical reasons, blood tests that had been originally planned were not performed and 12-month follow-up was available for only a small proportion.Results At 6 weeks, cycle endurance time increased from 377 (140) s to 787 (343) s with PR vs 495 (171) s to 479 (159) s for usual care, effect size +383 (231) s (p<0.001). PR also improved 6 min walk distance+103.2 m (63.6–142.9) (p<0.001), MRC dyspnoea score −0.36 (−0.65 to −0.07) (p=0.016) and quality of life; SGRQ −8.43 (−13.38 to −3.48) p<0.001, as well as quadriceps strength+9.28 Nm (1.89 to 16.66) p=0.015.Conclusion These data suggest that PR can improve exercise capacity and quality of life in people with breathlessness due to mustard gas lung disease and support the wider provision of this form of care.Trial registration number IRCT2016051127848N1.
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Book chapterNucera F, Bonina L, Cipolla A, et al., 2024,
Poxviridae Pneumonia
, Poxviruses, Editors: Rezaei, Publisher: Springer, Cham, Pages: 183-204, ISBN: 978-3-031-57165-7Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral pneumonia (with or without bacterial superinfections). Historically variola virus has been the poxviridae most frequently associated with the development of pneumonia with many large outbreaks worldwide before its eradication in 1980. It is still considered a biological threat for its potential in biological warfare and bioterrorism. Smallpox pneumonia can be severe with the onset of acute respiratory distress syndrome (ARDS) and death. Vaccinia virus, used for vaccination against smallpox exceptionally, in immunocompromised patients, can induce generalized (with also lung involvement) severe disease after vaccination. MPXV virus occasionally can cause pneumonia particularly in immunocompromised patients. The pathophysiology of poxviridae pneumonia is still an area of active research; however, in animal models these viruses can cause both direct damage to the lower airways epithelium and a hyperinflammatory syndrome, like a cytokine storm. Multiple mechanisms of immune evasion have also been described. The treatment of poxviridae pneumonia is mainly based on careful supportive care. Despite the absence of randomized clinical trials in patients with poxviridae pneumonia there are antiviral drugs, such as tecovirimat, cidofovir and brincidofovir, FDA-approved for use in smallpox and also available under an expanded access protocol for treatment of MPXV. There are 2 (replication-deficient modified vaccinia Ankara and replication-competent vaccinia virus) smallpox vaccines FDA-approved with the first one also approved for prevention of MPXV in adults that are at high risk of infection.
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Journal articleAgache I, Ricci-Cabello I, Canelo-Aybar C, et al., 2024,
The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma
, ALLERGY, ISSN: 0105-4538 -
Journal articleCheng S, Hedges M, Keski-Rahkonen P, et al., 2024,
Multiomic signatures of traffic related air pollution in London reveal potential short-term perturbations in gut microbiome-related pathways
, Environmental Science and Technology (Washington), Vol: 58, Pages: 8771-8782, ISSN: 0013-936XThis randomized crossover study investigated the metabolic and mRNA alterations associated with exposure to high and low traffic-related air pollution (TRAP) in 50 participants who were either healthy or were diagnosed with chronic pulmonary obstructive disease (COPD) or ischemic heart disease (IHD). For the first time, this study combined transcriptomics and serum metabolomics measured in the same participants over multiple time points (2 h before, and 2 and 24 h after exposure) and over two contrasted exposure regimes to identify potential multiomic modifications linked to TRAP exposure. With a multivariate normal model, we identified 78 metabolic features and 53 mRNA features associated with at least one TRAP exposure. Nitrogen dioxide (NO2) emerged as the dominant pollutant, with 67 unique associated metabolomic features. Pathway analysis and annotation of metabolic features consistently indicated perturbations in the tryptophan metabolism associated with NO2 exposure, particularly in the gut-microbiome-associated indole pathway. Conditional multiomics networks revealed complex and intricate mechanisms associated with TRAP exposure, with some effects persisting 24 h after exposure. Our findings indicate that exposure to TRAP can alter important physiological mechanisms even after a short-term exposure of a 2 h walk. We describe for the first time a potential link between NO2 exposure and perturbation of the microbiome-related pathways.
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Journal articleRitchie AI, Donaldson GC, Hoffman EA, et al., 2024,
Structural predictors of lung function decline in young smokers with normal spirometry
, American Journal of Respiratory and Critical Care Medicine, Vol: 209, Pages: 1208-1218, ISSN: 1073-449XRationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred.Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time.Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT.Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability–defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score.Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression.
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Journal articleFung LWY, Yan VKC, Kwan C, et al., 2024,
SABINA plus Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting β2 agonists in the Chinese population
, BMC PULMONARY MEDICINE, Vol: 24, ISSN: 1471-2466 -
Journal articleMakrufardi F, Chuang H-C, Suk C-W, et al., 2024,
Particulate matter deposition and its impact on tuberculosis severity: A cross-sectional study in Taipei
, SCIENCE OF THE TOTAL ENVIRONMENT, Vol: 924, ISSN: 0048-9697 -
Journal articleLaiman V, Chuang H-C, Lo Y-C, et al., 2024,
Cigarette smoke-induced dysbiosis: comparative analysis of lung and intestinal microbiomes in COPD mice and patients
, RESPIRATORY RESEARCH, Vol: 25 -
Journal articleNoakes FF, Smitten KL, Maple LEC, et al., 2024,
Phenazine cations as anticancer theranostics
, Journal of the American Chemical Society, Vol: 146, Pages: 12836-12849, ISSN: 0002-7863The biological properties of two water-soluble organic cations based on polypyridyl structures commonly used as ligands for photoactive transition metal complexes designed to interact with biomolecules are investigated. A cytotoxicity screen employing a small panel of cell lines reveals that both cations show cytotoxicity toward cancer cells but show reduced cytotoxicity to noncancerous HEK293 cells with the more extended system being notably more active. Although it is not a singlet oxygen sensitizer, the more active cation also displayed enhanced potency on irradiation with visible light, making it active at nanomolar concentrations. Using the intrinsic luminescence of the cations, their cellular uptake was investigated in more detail, revealing that the active compound is more readily internalized than its less lipophilic analogue. Colocalization studies with established cell probes reveal that the active cation predominantly localizes within lysosomes and that irradiation leads to the disruption of mitochondrial structure and function. Stimulated emission depletion (STED) nanoscopy and transmission electron microscopy (TEM) imaging reveal that treatment results in distinct lysosomal swelling and extensive cellular vacuolization. Further imaging-based studies confirm that treatment with the active cation induces lysosomal membrane permeabilization, which triggers lysosome-dependent cell-death due to both necrosis and caspase-dependent apoptosis. A preliminary toxicity screen in the Galleria melonella animal model was carried out on both cations and revealed no detectable toxicity up to concentrations of 80 mg/kg. Taken together, these studies indicate that this class of synthetically easy-to-access photoactive compounds offers potential as novel therapeutic leads.
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Journal articlePhilip K, Buttery S, Bowen S, et al., 2024,
Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery
, BMJ Open Respiratory Research, Vol: 11, ISSN: 2052-4439Background Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach.Methods We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores.Results We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62–74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3–4), forced expiratory volume in 1 s % predicted 49 (35–63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI −1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403).Discussion and conclusion A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful.Trial registration number NCT04034212.
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Conference paperThillai M, Oldham J, Ruggiero A, et al., 2024,
Deep Learning-based Segmentation of CT Scans Predicts Disease Progression and Mortality in IPF
, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X -
Conference paperDoffman S, Dosanjh D, Sadiq M, et al., 2024,
Phase 1 Safety and Efficacy of AZD8630/AMG 104 Inhaled Anti-TSLP in Healthy Volunteers and Patients With Asthma on Medium-High Dose Inhaled Corticosteroid (ICS) and Long-Acting Beta-agonist (LABA) With Elevated Baseline Fractional Exhaled Nitric Oxide (FeNO)
, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X -
Conference paperOwen CA, Zhou X, Sobande O, et al., 2024,
A First-in-human Study in Healthy Volunteers Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5055, A Novel Oral Porcupine Inhibitor Under Development as a Treatment for Pulmonary Fibrosis
, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X -
Conference paperSmall P, Rudd M, Chung KF, 2024,
Cough-omics: Quantifying the Variability and Predictability of Daily Cough Countsin Persistent Coughers
, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X -
Journal articleBloom CI, 2024,
Reply: Asthma and cardiovascular disease: the strength of triangulation
, EUROPEAN RESPIRATORY JOURNAL, Vol: 63, ISSN: 0903-1936 -
Conference paperRaby K, Dixey P, Versi A, et al., 2024,
Mechanisms of Nasal Epithelial Cell Permeability in Eosinophilic Severe Asthma: Effect of Anti-IL5R Therapy
, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X -
Conference paperRitchie AI, Hoffman EA, Allinson JP, et al., 2024,
Structural Predictors of Lung Function Decline in the British Early COPD Network (BEACON) Cohort
, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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