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BMJ Open Respiratory Research Mar 2024The plethysmographic shift volume-flow loop (sR-loop) measured during tidal breathing allows the determination of several lung function parameters such as the effective...
Predicting parameters of airway dynamics generated from inspiratory and expiratory plethysmographic airway loops, differentiating subtypes of chronic obstructive diseases.
BACKGROUND
The plethysmographic shift volume-flow loop (sR-loop) measured during tidal breathing allows the determination of several lung function parameters such as the effective specific airway resistance (sR), calculated from the ratio of the integral of the resistive aerodynamic specific work of breathing (sWOB) and the integral of the corresponding flow-volume loop. However, computing the inspiratory and expiratory areas of the sR-loop separately permits the determination of further parameters of airway dynamics. Therefore, we aimed to define the discriminating diagnostic power of the inspiratory and expiratory sWOB (sWOB, sWOB), as well as of the inspiratory and expiratory sR (sR and sR ), for discriminating different functional phenotypes of chronic obstructive lung diseases.
METHODS
Reference equations were obtained from measurement of different databases, incorporating 194 healthy subjects (35 children and 159 adults), and applied to a collective of 294 patients with chronic lung diseases (16 children with asthma, aged 6-16 years, and 278 adults, aged 17-92 years). For all measurements, the same type of plethysmograph was used (Jaeger Würzburg, Germany).
RESULTS
By multilinear modelling, reference equations of sWOB, sWOB, sR and sR were derived. Apart from anthropometric indices, additional parameters such as tidal volume (V), the respiratory drive (P), measured by means of a mouth occlusion pressure measurement 100 ms after inspiration and the mean inspiratory flow (V/T) were found to be informative. The statistical approach to define reference equations for parameters of airway dynamics reveals the interrelationship between covariants of the actual breathing pattern and the control of breathing.
CONCLUSIONS
We discovered that sWOB, sWOB, sR and sR are new discriminating target parameters, that differentiate much better between chronic obstructive diseases and their subtypes, especially between chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO), thus strengthening the concept of precision medicine.
Topics: Adult; Child; Humans; Respiration; Pulmonary Disease, Chronic Obstructive; Exhalation; Respiratory Function Tests; Asthma
PubMed: 38460977
DOI: 10.1136/bmjresp-2023-002142 -
Intensive Care Medicine Experimental Mar 2024Aim of this study was to evaluate feasibility and effects of individualised flow-controlled ventilation (FCV), based on compliance guided pressure settings, compared to...
BACKGROUND
Aim of this study was to evaluate feasibility and effects of individualised flow-controlled ventilation (FCV), based on compliance guided pressure settings, compared to standard of pressure-controlled ventilation (PCV) in a porcine intra-abdominal hypertension (IAH) model. The primary aim of this study was to investigate oxygenation. Secondary aims were to assess respiratory and metabolic variables and lung tissue aeration.
METHODS
Pigs were randomly assigned to FCV (n = 9) and PCV (n = 9). IAH was induced by insufflation of air into the abdomen to induce IAH grades ranging from 0 to 3. At each IAH grade FCV was undertaken using compliance guided pressure settings, or PCV (n = 9) was undertaken with the positive end-expiratory pressure titrated for maximum compliance and the peak pressure set to achieve a tidal volume of 7 ml/kg. Gas exchange, ventilator settings and derived formulas were recorded at two timepoints for each grade of IAH. Lung aeration was assessed by a computed tomography scan at IAH grade 3.
RESULTS
All 18 pigs (median weight 54 kg [IQR 51-67]) completed the observation period of 4 h. Oxygenation was comparable at each IAH grade, but a significantly lower minute volume was required to secure normocapnia in FCV at all IAH grades (7.6 vs. 14.4, MD - 6.8 (95% CI - 8.5 to - 5.2) l/min; p < 0.001). There was also a significant reduction of applied mechanical power being most evident at IAH grade 3 (25.9 vs. 57.6, MD - 31.7 (95% CI - 39.7 to - 23.7) J/min; p < 0.001). Analysis of Hounsfield unit distribution of the computed tomography scans revealed a significant reduction in non- (5 vs. 8, MD - 3 (95% CI - 6 to 0) %; p = 0.032) and poorly-aerated lung tissue (7 vs. 15, MD - 6 (95% CI - 13 to - 3) %, p = 0.002) for FCV. Concomitantly, normally-aerated lung tissue was significantly increased (84 vs. 76, MD 8 (95% CI 2 to 15) %; p = 0.011).
CONCLUSIONS
Individualised FCV showed similar oxygenation but required a significantly lower minute volume for CO-removal, which led to a remarkable reduction of applied mechanical power. Additionally, there was a shift from non- and poorly-aerated lung tissue to normally-aerated lung tissue in FCV compared to PCV.
PubMed: 38451347
DOI: 10.1186/s40635-024-00608-9 -
BMC Pulmonary Medicine Mar 2024Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small...
BACKGROUND
Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD.
METHODS
A total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO, FeNO, and calculated CaNO. Both FeNO and CaNO were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD.
RESULTS
Exhaled NO levels (FnNO, FeNO, FeNO, and CaNO) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO, FeNO, and CaNO) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNO (AUC ROC = 0.707) in COPD. FeNO was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797-2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO and FeNO.
CONCLUSION
The complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels.
Topics: Humans; X-Ray Microtomography; Pulmonary Disease, Chronic Obstructive; Inflammation; Bronchitis, Chronic; Pulmonary Emphysema; Nitric Oxide
PubMed: 38443860
DOI: 10.1186/s12890-024-02911-3 -
Saudi Medical Journal Mar 2024Lung cancer is a complicated and challenging disease and is one of the most common causes of cancer-related mortality worldwide. Within the lung microenvironment,... (Review)
Review
Lung cancer is a complicated and challenging disease and is one of the most common causes of cancer-related mortality worldwide. Within the lung microenvironment, specific cytokines, including the B cell activation factor (BAFF) and the A proliferation-inducing ligand (APRIL), are produce by various cells, notably airway epithelial cells, in response allergic inflammation or pulmonary infection. These cytokines play a critical role in maintaining local immune responses and fostering the survival of immune cells. The BAFF and APRIL system have been connected in a range of malignancies and have shown their potential in inducing drug resistance and promoting cancer progression. This review highlights recent studies on the involvement of BAFF and APRIL in various cancers, focusing mainly on their role in lung cancer, and discusses the possibility of these molecules in contributing to drug resistance and cancer progression following pulmonary infection. We suggest consideration the targeting BAFF and APRIL or their respective receptors as promising novel therapies for effective treatment of lung cancer, especially post pulmonary infection. However, it remains important to conduct further investigations to fully elucidate the precise mechanisms underlying how the BAFF and APRIL systems enhance cancer survival and drug resistance subsequent pulmonary infections.
Topics: Humans; Lung Neoplasms; Ligands; Pneumonia; Cytokines; Immunity; Tumor Microenvironment
PubMed: 38438201
DOI: 10.15537/smj.2024.45.3.20230873 -
Journal of Equine Veterinary Science Apr 2024Equine asthma (EA) is a respiratory syndrome associated with the increase of different leukocyte populations in the bronchoalveolar lavage fluid (BALF). Its pathogenetic...
Equine asthma (EA) is a respiratory syndrome associated with the increase of different leukocyte populations in the bronchoalveolar lavage fluid (BALF). Its pathogenetic mechanisms remain unclear. This study aimed to evaluate the associations between the mRNA expression of different cytokines in the BALF, different EA subtypes and lung function. Fifteen horses underwent physical examination, airway endoscopy, BALF cytology and lung function testing (8/15). One horse did not have evidence of EA and was used as healthy reference, while the others were classified as affected by neutrophilic or mixed granulocytic EA. Cells isolated from the residual BALF were used for IL-1β, IL-2, IFN-γ, IL-4, IL-17A genes expression by quantitative RT-PCR., Cytokine expression was compared between groups, and their correlations with BALF leukocyte and lung function were evaluated. IL-1β expression was positively correlated with BALF neutrophils count (p=0.038, r=0.56) and with increased expiratory resistance (p=0.047, r=0.76). IFN-γ was correlated with BALF mast cells (p=0.029, r=0.58). IL-4 was higher in horses with mixed granulocytic EA than neutrophilic (p=0.008), positively correlated with BALF mast cells (p=0.028, r=0.59) and inversely with whole-breath (p=0.046, r=-0.76) and expiratory reactance (p=0.003, r=-0.93). Finally, IL-17A was inversely correlated with expiratory reactance (p=0.009, r=-0.92). These results support that multiple immune responses are involved in EA pathogenesis; innate, Th2, and Th17 responses. Innate immunity appeared associated with neutrophilic inflammation, and Th2 response with increased mast cells. The role of Th1 response in EA remains questionable.
Topics: Horses; Animals; Cytokines; Interleukin-17; Interleukin-4; Bronchoalveolar Lavage; Asthma; RNA, Messenger; Horse Diseases
PubMed: 38423374
DOI: 10.1016/j.jevs.2024.105033 -
European Respiratory Review : An... Jan 2024There is an increased risk of adverse perinatal outcomes in the ∼17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes...
There is an increased risk of adverse perinatal outcomes in the ∼17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes are largely unknown, but reflect joint effects of genetics and prenatal exposure to maternal asthma. Animal models are essential to understand the underlying mechanisms independent of genetics and comorbidities, and enable safe testing of interventions. This scoping review aimed to explore the methodology, phenotype, characteristics, outcomes and quality of published studies using preclinical maternal asthma models. MEDLINE (PubMed), Embase (Elsevier) and Web of Science were systematically searched using previously validated search strings for maternal asthma and for animal models. Two reviewers independently screened titles and abstracts, full texts, and then extracted and assessed the quality of each study using the Animal Research: Reporting of Experiments (ARRIVE) 2.0 guidelines. Out of 3618 studies identified, 39 were eligible for extraction. Most studies were in rodents (86%) and all were models of allergic asthma. Maternal and progeny outcomes included airway hyperresponsiveness, airway resistance, inflammation, lung immune cells, lung structure and serum immunoglobulins and cytokines. Experimental design (100%), procedural details (97%) and rationale (100%) were most often reported. Conversely, data exclusion (21%), blinding (18%) and adverse events (8%) were reported in a minority of studies. Species differences in physiology and timing of development, the use of allergens not relevant to humans and a lack of comparable outcome measures may impede clinical translation. Future studies exploring models of maternal asthma should adhere to the minimum core outcomes set presented in this review.
Topics: Animals; Female; Humans; Pregnancy; Asthma; Pregnancy Complications
PubMed: 38417970
DOI: 10.1183/16000617.0174-2023 -
Cureus Jan 2024Attention to physical activity has grown in patients with chronic obstructive pulmonary disease (COPD), as it serves as a robust indicator for mortality associated with...
BACKGROUND
Attention to physical activity has grown in patients with chronic obstructive pulmonary disease (COPD), as it serves as a robust indicator for mortality associated with COPD. Non-exercise activity thermogenesis (NEAT) is the energy expenditure due to physical activities besides active sports-like exercises and resistance training in daily life, and decreased NEAT may be related to physical inactivity in patients with COPD. We examined whether NEAT assessed using a questionnaire reflects clinical parameters in patients with or at risk for COPD.
METHODS
The study participants consisted of 36 male patients (COPD=28; stage1=6, stage2=14, stage3/4=8, and at-risk for COPD=8) older than 50 years of age. The participants underwent anthropometric measurements, lung function testing, a six-minute walk test, muscle strength testing, and questionnaires, e.g., the COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and Hospital Anxiety and Depression Scale. Image analysis with chest computed tomography (CT) included the number of trunk muscles, bronchial wall thickening, and emphysema (percentage of the lung field occupied by low attenuation area <-950 HU). We evaluated the relationship between these clinical parameters and NEAT questionnaire scores using Pearson correlation analysis and the Tukey-Kramer test.
RESULTS
The NEAT score was correlated with the severity of airflow limitation and airway wall thickness measured by chest CT, symptoms evaluated by the mMRC dyspnea scale and CAT, and inspiratory muscle strength and pectoralis muscle area assessed by CT.
CONCLUSION
Our study revealed the significance of NEAT as a valuable indicator in assessing the health status of patients with or at risk for COPD. The NEAT score was correlated with various clinical traits, suggesting that incorporating NEAT assessments using a questionnaire can contribute to a comprehensive understanding of the clinical condition in these patients. Further large-scale studies are warranted to validate and generalize these findings across diverse COPD populations.
PubMed: 38410298
DOI: 10.7759/cureus.53019 -
Scientific Reports Feb 2024Airborne transmission of pathogens plays a major role in the spread of infectious diseases. Aerosol particle production from the lung is thought to occur in the...
Airborne transmission of pathogens plays a major role in the spread of infectious diseases. Aerosol particle production from the lung is thought to occur in the peripheral airways. In the present study we investigated eighty lung-healthy subjects of two age groups (20-39, 60-76 years) at rest and during exercise whether lung function parameters indicative of peripheral airway function were correlated with individual differences in aerosol particle emission. Lung function comprised spirometry and impulse oscillometry during quiet breathing and an expiratory vital capacity manoeuvre, using resistance (R5) and reactance at 5 Hz (X5) as indicators potentially related to peripheral airway function. The association between emission at different ventilation rates relative to maximum ventilation and lung function was assessed by regression analysis. In multiple regression analyses including age group, only vital capacity manoeuvre R5 at 15% to 50% of end-expiratory vital capacity as well as quiet breathing X5 were independently linked to particle emission at 20% to 50% of maximum ventilation, in addition to age group. The fact that age as predictive factor was still significant, although to a lower degree, points towards further effects of age, potentially involving surface properties not accounted for by impulse oscillometry parameters.
Topics: Humans; Young Adult; Adult; Airway Resistance; Oscillometry; Lung; Respiratory Function Tests; Spirometry; Forced Expiratory Volume
PubMed: 38409397
DOI: 10.1038/s41598-024-55117-2 -
Respirology (Carlton, Vic.) Apr 2024
Topics: Humans; Asthma; Eosinophilia; Respiratory System
PubMed: 38403834
DOI: 10.1111/resp.14685 -
Respiratory Research Feb 2024Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing...
BACKGROUND
Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children.
METHODS
History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R), frequency-dependence of resistance (R), reactance at 7 Hz (X), area of the reactance curve (AX), end-inspiratory and end-expiratory R (R, R) and X (X, X), and volume-dependence of resistance (ΔR = R-R) was estimated by linear regression adjusted on confounders.
RESULTS
Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher R, R, ΔR and R and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R and AX and lower X and bronchitis with higher R. No statistically significant association was observed for hospitalisation.
CONCLUSIONS
Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.
Topics: Humans; Child, Preschool; Respiratory Sounds; Spirometry; Respiratory System; Asthma; Respiratory Mechanics; Bronchiolitis; Bronchitis
PubMed: 38402379
DOI: 10.1186/s12931-024-02701-9