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Chest Nov 2023Studies examining agreement between home and clinic spirometry in patients with asthma are limited, with conflicting results. Understanding the strengths and limitations... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Studies examining agreement between home and clinic spirometry in patients with asthma are limited, with conflicting results. Understanding the strengths and limitations of telehealth and home spirometry is particularly important considering the SARS-CoV-2 pandemic.
RESEARCH QUESTION
How well do home and clinic measurements of trough FEV agree in patients with uncontrolled asthma?
STUDY DESIGN AND METHODS
This post hoc analysis used trough FEV data from the randomized double-anonymized parallel-group phase 3A CAPTAIN (205715; NCT02924688) and phase 2B 205832 (NCT03012061) trials in patients with uncontrolled asthma. CAPTAIN evaluated the impact of adding umeclidinium to fluticasone furoate/vilanterol via a single inhaler; the 205832 trial investigated adding umeclidinium to fluticasone furoate vs placebo. Trough FEV measurements were collected via home spirometry and supervised in-person spirometry in the research clinic. To compare home and clinic spirometry, we examined the time-course analyses of home and clinic trough FEV, and generated post hoc Bland-Altman plots to assess agreement between home and clinic spirometry.
RESULTS
Data from 2,436 patients (CAPTAIN trial) and 421 patients (205832 trial) were analyzed. Treatment-related improvements in FEV were observed in both trials, using home and clinic spirometry. Improvements measured by home spirometry were of lower magnitude and less consistent than clinic measurements. Bland-Altman plots suggested poor agreement between home and clinic trough FEV at baseline and week 24.
INTERPRETATION
This post hoc comparison of home and clinic spirometry is the largest conducted in asthma. Results showed that home spirometry was less consistent than and lacked agreement with clinic spirometry, suggesting that unsupervised home readings are not interchangeable with clinic measurements. However, these findings may only be applicable to home spirometry using the specific device and coaching methods employed in these studies. Postpandemic, further research to optimize home spirometry use is needed.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov; Nos.: NCT03012061 and NCT02924688; URL: www.
CLINICALTRIALS
gov.
Topics: Humans; Administration, Inhalation; Asthma; Bronchodilator Agents; Chlorobenzenes; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Lung; Nebulizers and Vaporizers; Spirometry; Treatment Outcome
PubMed: 37385337
DOI: 10.1016/j.chest.2023.06.029 -
Current Biology : CB Aug 2023In the 1880s, Henri Fabre was captivated by the "special art of eating", whereby a parasitoid wasp larva fed selectively on host internal organs, avoiding the heart...
In the 1880s, Henri Fabre was captivated by the "special art of eating", whereby a parasitoid wasp larva fed selectively on host internal organs, avoiding the heart (dorsal vessel) and tracheal system (respiratory system) to preserve life. In Fabre's words: "The ruling feature in this scientific method of eating, which proceeds from parts less to the parts more necessary to preserve a remnant of life, is none the less obvious". Subsequent investigators have reported the same for many parasitoid wasps, including for the emerald jewel wasp (Ampulex compressa). Here it is reported that larval jewel wasps destroy the dorsal vessel and tracheae (respiratory system) in the thorax of their cockroach host (Periplaneta americana) at their earliest opportunity. Moreover, the broken tracheae release air into the host, which the larval jewel wasp inspires. An increase in larval chewing rate, cotemporaneous with the sudden release of air from the host's broken tracheae, suggests the larva taps into the host respiratory system to support its metabolism while rapidly consuming the host. VIDEO ABSTRACT.
Topics: Animals; Wasps; Cockroaches; Larva; Wasp Venoms; Host-Parasite Interactions; Respiratory System; Thorax
PubMed: 37552942
DOI: 10.1016/j.cub.2023.06.005 -
Cell Stem Cell Apr 2024The respiratory system acts as both the primary site of gas exchange and an important sensor and barrier to the external environment. The increase in incidences of... (Review)
Review
The respiratory system acts as both the primary site of gas exchange and an important sensor and barrier to the external environment. The increase in incidences of respiratory disease over the past decades has highlighted the importance of developing improved therapeutic approaches. This review will summarize recent research on the cellular complexity of the mammalian respiratory system with a focus on gas exchange and immunological defense functions of the lung. Different models of repair and regeneration will be discussed to help interpret human and animal data and spur the investigation of models and assays for future drug development.
Topics: Animals; Humans; Lung; Mammals
PubMed: 38492572
DOI: 10.1016/j.stem.2024.02.009 -
The Lancet. Child & Adolescent Health Aug 2023Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population.
METHODS
PICSI was a randomised, double-blind, placebo-controlled trial at Perth Children's Hospital (Perth, WA, Australia) to assess whether fluticasone propionate, an inhaled corticosteroid, improves lung function in children who had been born very preterm (<32 weeks of gestation). Eligible children were aged 6-12 years and did not have severe congenital abnormalities, cardiopulmonary defects, neurodevelopmental impairment, diabetes, or any glucocorticoid use within the preceding 3 months. Participants were randomly assigned (1:1) to receive 125 μg fluticasone propionate or placebo twice daily for 12 weeks. Participants were stratified for sex, age, bronchopulmonary dysplasia diagnosis, and recent respiratory symptoms using the biased-coin minimisation technique. The primary outcome was change in pre-bronchodilator forced expiratory volume in 1 s (FEV) after 12 weeks of treatment. Data were analysed by intention-to-treat (ie, all participants who were randomly assigned and took at least the tolerance dose of the drug). All participants were included in the safety analyses. This trial is registered at the Australian and New Zealand Clinical Trials Registry, number 12618000781246.
FINDINGS
Between Oct 23, 2018, and Feb 4, 2022, 170 participants were randomly assigned and received at least the tolerance dose (83 received placebo and 87 received inhaled corticosteroid). 92 (54%) participants were male and 78 (46%) were female. 31 participants discontinued treatment before 12 weeks (14 in the placebo group and 17 in the inhaled corticosteroid group), mostly due to the impact of the COVID-19 pandemic. When analysed by intention-to-treat, the change in pre-bronchodilator FEV Z score over 12 weeks was -0·11 (95% CI -0·21 to 0·00) in the placebo group and 0·20 (0·11 to 0·30) in the inhaled corticosteroid group (imputed mean difference 0·30, 0·15-0·45). Three of 83 participants in the inhaled corticosteroid group had adverse events requiring treatment discontinuation (exacerbation of asthma-like symptoms). One of 87 participants in the placebo group had an adverse event requiring treatment discontinuation (inability to tolerate the treatment with dizziness, headaches, stomach pains, and worsening of a skin condition).
INTERPRETATION
As a group, children born very preterm have only modestly improved lung function when treated with inhaled corticosteroid for 12 weeks. Future studies should consider individual phenotypes of lung disease after preterm birth and other agents to improve management of prematurity-associated lung disease.
FUNDING
Australian National Health and Medical Research Council, Telethon Kids Institute, and Curtin University.
Topics: Infant, Newborn; Male; Child; Humans; Female; Bronchodilator Agents; Infant, Extremely Premature; Pandemics; Australia; COVID-19; Premature Birth; Fluticasone; Adrenal Cortex Hormones; Lung
PubMed: 37385269
DOI: 10.1016/S2352-4642(23)00128-1 -
Current Opinion in Pulmonary Medicine May 2024Bronchiectasis is a chronic respiratory disease characterized by dilated airways, persistent sputum production and recurrent infective exacerbations. The microbiology of... (Review)
Review
PURPOSE OF REVIEW
Bronchiectasis is a chronic respiratory disease characterized by dilated airways, persistent sputum production and recurrent infective exacerbations. The microbiology of bronchiectasis includes various potentially pathogenic microorganisms including Pseudomonas aeruginosa which is commonly cultured from patients' sputum. P. aeruginosa is difficult to eradicate and frequently exhibits antimicrobial resistance. Bacteriophage therapy offers a novel and alternative method to treating bronchiectasis and can be used in conjunction with antibiotics to improve patient outcome.
RECENT FINDINGS
Thirteen case reports/series to date have successfully used phages to treat infections in bronchiectasis patients, however these studies were constrained to few patients ( n = 32) and utilized personalized phage preparations and adjunct antibiotics. In these studies, phage therapy was delivered by inhalation, intravenously or orally and was well tolerated in most patients without any unfavourable effects. Favourable clinical or microbiological outcomes were seen following phage therapy in many patients. Longitudinal patient follow-up reported regrowth of bacteria and phage neutralization in some studies. There are five randomized clinical controlled trials ongoing aiming to use phage therapy to treat P. aeruginosa associated respiratory conditions, with limited results available to date.
SUMMARY
More research, particularly robust clinical trials, into how phages can clear respiratory infections, interact with resident microbiota, and how bacteria might develop resistance will be important to establish to ensure the success of this promising therapeutic alternative.
Topics: Humans; Bacteriophages; Anti-Bacterial Agents; Bronchiectasis; Pseudomonas Infections; Respiratory System; Pseudomonas aeruginosa
PubMed: 38345396
DOI: 10.1097/MCP.0000000000001050 -
Biological Reviews of the Cambridge... Dec 2023In commercial poultry farming, respiratory diseases cause high morbidities and mortalities, begetting colossal economic losses. Without empirical evidence, early... (Review)
Review
A critical assessment of the cellular defences of the avian respiratory system: are birds in general and poultry in particular relatively more susceptible to pulmonary infections/afflictions?
In commercial poultry farming, respiratory diseases cause high morbidities and mortalities, begetting colossal economic losses. Without empirical evidence, early observations led to the supposition that birds in general, and poultry in particular, have weak innate and adaptive pulmonary defences and are therefore highly susceptible to injury by pathogens. Recent findings have, however, shown that birds possess notably efficient pulmonary defences that include: (i) a structurally complex three-tiered airway arrangement with aerodynamically intricate air-flow dynamics that provide efficient filtration of inhaled air; (ii) a specialised airway mucosal lining that comprises air-filtering (ciliated) cells and various resident phagocytic cells such as surface and tissue macrophages, dendritic cells and lymphocytes; (iii) an exceptionally efficient mucociliary escalator system that efficiently removes trapped foreign agents; (iv) phagocytotic atrial and infundibular epithelial cells; (v) phagocytically competent surface macrophages that destroy pathogens and injurious particulates; (vi) pulmonary intravascular macrophages that protect the lung from the vascular side; and (vii) proficiently phagocytic pulmonary extravasated erythrocytes. Additionally, the avian respiratory system rapidly translocates phagocytic cells onto the respiratory surface, ostensibly from the subepithelial space and the circulatory system: the mobilised cells complement the surface macrophages in destroying foreign agents. Further studies are needed to determine whether the posited weak defence of the avian respiratory system is a global avian feature or is exclusive to poultry. This review argues that any inadequacies of pulmonary defences in poultry may have derived from exacting genetic manipulation(s) for traits such as rapid weight gain from efficient conversion of food into meat and eggs and the harsh environmental conditions and severe husbandry operations in modern poultry farming. To reduce pulmonary diseases and their severity, greater effort must be directed at establishment of optimal poultry housing conditions and use of more humane husbandry practices.
Topics: Animals; Poultry; Birds; Lung; Phagocytes; Erythrocytes
PubMed: 37489059
DOI: 10.1111/brv.13000 -
The Journal of Maternal-fetal &... Dec 2023Respiratory distress syndrome (RDS) is a common critical lung disease in newborn infants, especially those in premature infants with higher mortality rate. Early and...
Respiratory distress syndrome (RDS) is a common critical lung disease in newborn infants, especially those in premature infants with higher mortality rate. Early and correct diagnosis is the key to improve its prognosis. Previously, the diagnosis of RDS mainly relied on chest X-ray (CXR) findings, and it has been graded into four stages based on the progression and severity of CXR changes. This traditional diagnosing and grading method may lead to high misdiagnosis rate or delayed diagnosis. Recently, using ultrasound to diagnose neonatal lung diseases and RDS is becoming increasingly popular, and the technology is gaining higher sensitivity and higher specificity. The management of RDS under lung ultrasound (LUS) monitoring has achieved significant results, reducing the misdiagnosis rate of RDS, thereby reducing the probability of mechanical ventilation and the use of exogenous pulmonary surfactant, and making the success rate of treatment of RDS up to 100%. The purpose of the article was to introduce the ultrasound grading methods and criteria of RDS, in order to promote the application of LUS in the diagnosis and treatment of RDS. Literature (in English and Chinese) on the use of ultrasound in the diagnosis of neonatal RDS between 2008 and 2022 was selected for inclusion in this study. From the collected literature, the use of ultrasound in the diagnosis of RDS is increasing, and people's understanding of the ultrasound imaging findings of RDS is also changing. Among them, the research on ultrasound grading of RDS is the latest progress. Ultrasound is accurate and reliable in the diagnosis and differential diagnosis of RDS. It is of great clinical value to master the ultrasound diagnosis and grading criteria of RDS.
Topics: Infant, Newborn; Humans; Respiratory Distress Syndrome, Newborn; Lung; Infant, Premature; Pulmonary Surfactants; Lung Diseases; Ultrasonography
PubMed: 37142428
DOI: 10.1080/14767058.2023.2206943 -
Immunological Reviews Aug 2023The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the... (Review)
Review
The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar compartments. We have reported that one of the most dominant molecular species of PG, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and PI inhibit inflammatory responses induced by multiple toll-like receptors (TLR2/1, TLR3, TLR4, and TLR2/6) by interacting with subsets of multiprotein receptor components. These lipids also exert potent antiviral effects against RSV and influenza A, in vitro, by inhibiting virus binding to host cells. POPG and PI inhibit these viral infections in vivo, in multiple animal models. Especially noteworthy, these lipids markedly attenuate SARS-CoV-2 infection including its variants. These lipids are natural compounds that already exist in the lung and, thus, are less likely to cause adverse immune responses by hosts. Collectively, these data demonstrate that POPG and PI have strong potential as novel therapeutics for applications as anti-inflammatory compounds and preventatives, as treatments for broad ranges of RNA respiratory viruses.
Topics: Animals; Humans; Phospholipids; Pulmonary Surfactants; Antiviral Agents; Toll-Like Receptor 2; COVID-19; SARS-CoV-2; Lung; Anti-Inflammatory Agents; Phosphatidylglycerols
PubMed: 37144896
DOI: 10.1111/imr.13207 -
Trials Nov 2023The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group.
METHODS/DESIGN
In this study, 668 spontaneously-breathing preterm infants, born at 25 to 29 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group.
DISCUSSION
Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.
Topics: Humans; Infant, Newborn; Bronchopulmonary Dysplasia; Continuous Positive Airway Pressure; Infant, Premature; Lung; Oxygen; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface-Active Agents; Ultrasonography, Interventional
PubMed: 37925512
DOI: 10.1186/s13063-023-07745-8 -
Journal of Aerosol Medicine and... Aug 2023The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for...
The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for measuring breath patterns and a formula for estimating inhaled drugs, and then to validate the hypothesized prediction formula. An model was first used to determine correlations among the delivered dose, breath patterns, and doses deposited on the accessories and reservoirs testing with a breathing simulator to generate 12 adult breathing patterns ( = 5). A pressure sensor was developed to measure breathing parameters and used along with a prediction formula that accounted for the initial charge dose, respiratory pattern, and dose on the accessory and reservoir of a nebulizer. Three brands of nebulizers were tested by placing salbutamol (5.0 mg/2.5 mL) in the drug holding chamber. Ten healthy individuals participated in the study to validate the prediction formula. The agreement between the predicted and inhaled doses was analyzed using the Bland-Altman plot. The model showed that the inspiratory time to total respiratory cycle time (/; %) was significantly directly correlated with the delivered dose among the respiratory factors, followed by inspiratory flow, respiratory rate, and tidal volume. The model showed that / was significantly directly correlated with the delivered dose among the respiratory factors, in addition to the nebulization time and accessory dose. The Bland-Altman plots for the model showed similar results between the two methods. Large differences in inhaled dose measured at the mouth were observed among the subjects, ranging from 12.68% to 21.68%; however, the difference between the predicted dose and inhaled dose was lower, at 3.98%-5.02%. The inhaled drug dose could be predicted with the hypothesized estimation formula, which was validated by the agreement between the inhaled and predicted doses of breathing patterns of healthy individuals.
Topics: Adult; Humans; Administration, Inhalation; Aerosols; Albuterol; Bronchodilator Agents; Equipment Design; Nebulizers and Vaporizers
PubMed: 37219568
DOI: 10.1089/jamp.2022.0055