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Lung Dec 2022The small airways dysfunction (SAD) asthma phenotype is characterised by narrowing of airways < 2 mm in diameter between generations 8 and 23 of the bronchial tree.... (Review)
Review
The small airways dysfunction (SAD) asthma phenotype is characterised by narrowing of airways < 2 mm in diameter between generations 8 and 23 of the bronchial tree. Recently, this has become particularly relevant as measurements of small airways using airway oscillometry for example, are strong determinants of asthma control and exacerbations in moderate-to-severe asthma. The small airways can be assessed using spirometry as forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF) and has been deemed more accurate in detecting small airways dysfunction than forced expiratory volume in 1 s (FEV). Oscillometry as the heterogeneity in resistance between 5 and 20 Hz (R5-R20), low frequency reactance at 5 Hz (X5) or area under the reactance curve between 5 Hz and the resonant frequency can also be used to assess the small airways. The small airways can also be assessed using the multiple breath nitrogen washout (MBNW) test giving rise to values including functional residual capacity, lung clearance index and ventilation distribution heterogeneity in the conducting (Scond) and the acinar (Sacin) airways. The ATLANTIS group showed that the prevalence of small airways disease in asthma defined on FEF, oscillometry and MBNW all increased with progressive GINA asthma disease stages. As opposed to topical inhaler therapy that might not adequately penetrate the small airways, it is perhaps more intuitive that systemic anti-inflammatory therapy with biologics targeting downstream cytokines and upstream epithelial anti-alarmins may offer a promising solution to SAD. Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma.
Topics: Humans; Asthma; Spirometry; Forced Expiratory Volume; Lung; Pulmonary Disease, Chronic Obstructive; Biological Therapy; Phenotype; Biological Products
PubMed: 36239786
DOI: 10.1007/s00408-022-00579-2 -
The Lancet. Respiratory Medicine Jul 2022Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the... (Observational Study)
Observational Study
BACKGROUND
Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life.
METHODS
In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed.
FINDINGS
773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0·20-0·25, p<0·0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life.
INTERPRETATION
Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations.
FUNDING
Chiesi Farmaceutici.
Topics: Asthma; Female; Forced Expiratory Volume; Humans; Longitudinal Studies; Male; Middle Aged; Oscillometry; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory System; Spirometry
PubMed: 35247313
DOI: 10.1016/S2213-2600(21)00536-1 -
Tuberculosis and Respiratory Diseases Apr 2022Post-tuberculosis (TB) sequelae is a commonly encountered clinical entity, especially in high TB burden countries. This may represent chronic anatomic sequelae of...
BACKGROUND
Post-tuberculosis (TB) sequelae is a commonly encountered clinical entity, especially in high TB burden countries. This may represent chronic anatomic sequelae of previously treated TB, with frequent symptomatic presentation. This pilot study was aimed to investigate the pulmonary functions and systemic inflammatory markers in patients with post-TB sequelae (PTBS) and to compare them with post-TB without sequelae (PTBWS) participants and healthy controls.
METHODS
A total of 30 participants were enrolled, PTBS (n=10), PTBWS (n=10), and healthy controls (n=10). Pulmonary function tests included spirometry and measurement of airway impedance by impulse oscillometry. Serum levels of matrix metalloproteinase (MMP)-1, transforming growth factor-β, and interferon-γ were estimated.
RESULTS
Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC, and peak expiratory flow were significantly lower in PTBS as compared to controls. SVC and FEV1 were significantly less in PTBS as compared to PTBWS. Total airway impedance (Z5), total airway resistance (R5), central airway resistance (R20), area of reactance (Ax), and resonant frequency (Fres) were significantly higher and respiratory reactance at 5 and 20 Hz (X5, X20) were significantly lower in PTBS as compared to PTBWS. Spirometry parameters correlated with impulse oscillometry parameters in PTBS. Serum MMP-1 level was significantly higher in PTBS as compared to other groups.
CONCLUSION
Significant pulmonary function impairment was observed in PTBS, and raised serum MMP-1 levels compared with PTBWS and healthy controls. Follow-up pulmonary function testing is recommended after treatment of TB for early diagnosis and treatment of PTBS.
PubMed: 35232004
DOI: 10.4046/trd.2021.0127 -
Respiratory Medicine Oct 2023Bronchial thermoplasty is an effective intervention to improve respiratory symptoms and to reduce the rate of exacerbations in uncontrolled severe asthma. A reduction in...
INTRODUCTION
Bronchial thermoplasty is an effective intervention to improve respiratory symptoms and to reduce the rate of exacerbations in uncontrolled severe asthma. A reduction in airway smooth muscle is arguably the most widely discussed mechanisms accounting for these clinical benefits. Yet, this smooth muscle reduction should also translate into an impaired response to bronchodilator drugs. This study was designed to address this question.
METHODS
Eight patients with clinical indication for thermoplasty were studied. They were uncontrolled severe asthmatics despite optimal environmental control, treatment of comorbidities, and the use of high-dose inhaled corticosteroids and long-acting β-agonists. Lung function measured by spirometry and respiratory mechanics measured by oscillometry were examined pre- and post-bronchodilator (salbutamol, 400 μg), both before and at least 1 year after thermoplasty.
RESULTS
Consistent with previous studies, thermoplasty yielded no benefits in terms of baseline lung function and respiratory mechanics, despite improving symptoms based on two asthma questionnaires (ACQ-5 and ACT-5). The response to salbutamol was also not affected by thermoplasty based on spirometric readouts, including forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), and FEV/FVC ratio. However, a significant interaction was observed between thermoplasty and salbutamol for two oscillometric readouts, namely reactance at 5 Hz (X) and reactance area (Ax), showing an attenuated response to salbutamol after thermoplasty.
CONCLUSIONS
Thermoplasty attenuates the response to a bronchodilator. We argue that this result is a physiological proof of therapeutic efficacy, consistent with the well-described effect of thermoplasty in reducing the amount of airway smooth muscle.
Topics: Humans; Bronchodilator Agents; Bronchial Thermoplasty; Asthma; Albuterol; Adrenal Cortex Hormones; Forced Expiratory Volume
PubMed: 37422022
DOI: 10.1016/j.rmed.2023.107340 -
Clinical Physiology and Functional... Jun 2024Expiratory flow limitation (EFL) during tidal breathing and lung hyperinflation have been identified as major decisive factors for disease status, prognosis and...
BACKGROUND
Expiratory flow limitation (EFL) during tidal breathing and lung hyperinflation have been identified as major decisive factors for disease status, prognosis and response to therapy in obstructive lung diseases.
AIM
To investigate the delta values between expiratory and inspiratory resistance and reactance, measured using respiratory oscillometry and its correlation with air trapping and symptoms in subjects with obstructive lung diseases.
METHODS
Four hundred and seventy-one subjects (96 with chronic obstructive pulmonary disease [COPD], 311 with asthma, 30 healthy smokers and 34 healthy subjects) were included. Spirometry, body plethysmography and respiratory oscillometry measurements were performed and the differences between the expiratory and inspiratory respiratory oscillometry values (as delta values) were calculated. Questionnaires regarding symptoms and quality of life were administered.
RESULTS
Patients with COPD and healthy smokers had an increased delta resistance at 5 Hz (R5) compared with patients with asthma (p < 0.0001 and p = 0.037, respectively) and healthy subjects (p = 0.0004 and p = 0.012, respectively). Patients with COPD also had higher values of ΔR5-R19 than healthy subjects (p = 0.0001) and patients with asthma (p < 0.0001). Delta reactance at 5 Hz (X5) was significantly more impaired in COPD patients than in asthma and healthy subjects (p < 0.0001 for all). There was a correlation between the ratio of residual volume and total lung capacity and ΔR5 (p = 0.0047; r = 0.32), ΔR5-R19 (p = 0.0002; r = 0.41) and ΔX5 (p < 0.0001; r = -0.44), for all subjects. ΔX5 correlated with symptoms in COPD, healthy smokers and patients with asthma. In addition, ΔR5 correlated with asthma symptoms.
CONCLUSION
EFL was most prominent in parameters measuring peripheral resistance and reactance and correlated with air trapping and airway symptoms.
PubMed: 38873744
DOI: 10.1111/cpf.12895 -
Indian Journal of Endocrinology and... 2023Obesity is known to induce lung function impairment. Previous studies of decline in lung function associated with obesity are well established.
BACKGROUND
Obesity is known to induce lung function impairment. Previous studies of decline in lung function associated with obesity are well established.
MATERIALS AND METHODS
In this cross-sectional study, to evaluate the effects of different obesity indices on lung mechanics, healthy subjects (males-23 and females-22) were recruited. Anthropometric parameters like body mass index (BMI), waist circumference (WC), hip circumference (HC) and neck circumference (NC) were measured and waist-hip ratio (WHR) was derived. Spirometry, impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) measurements were performed to assess lung function. Subgroups were divided and analysed.
RESULTS
In males, increased WHR is associated with increased total airway resistance (R). BMI correlates positively with R, R% predicted, resistance at 20 Hz (R) and R% predicted; likewise, WHR shows a positive correlation with R. In females, increased WHR has significantly higher R, R% predicted, R, R% predicted, area of reactance (Ax), resonant frequency (Fres) and decreased reactance at 5 Hz (X), reactance at 20 Hz (X), X% predicted. The female group with higher WC shows significantly increased R, R% predicted, R, R% predicted, Ax, Fres and lower fixed ratio of forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC), X, X, X% predicted. The group with higher NC has a lower FEV/FVC ratio. WHR positively correlated with R% predicted and Fres while WC correlated positively with R, R% predicted, Ax and Fres; same way, NC with X% predicted.
CONCLUSION
Obesity/overweight causes significant changes in lung volumes, capacity and airway mechanics, Higher WC and WHR are associated with significant changes in lung mechanics, which are more prominent in females than in males. NC is not associated with changes in lung mechanics.
PubMed: 37292068
DOI: 10.4103/ijem.ijem_363_22 -
Respiratory Research Mar 2022Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify Tc-hydroxy methylene diphosphonate (HMDP)...
BACKGROUND
Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify Tc-hydroxy methylene diphosphonate (HMDP) lung retention in hereditary transthyretin (ATTRv) cardiac amyloidosis patients and to relate tracer uptake intensity to pulmonary function and aerobic capacity.
METHODS
We prospectively enrolled 20 patients with biopsy-proven ATTRv cardiac amyloidosis and 20 control subjects. Cardiac involvement was confirmed by echocardiography and nuclear imaging using Tc-HMDP. Semi-quantitative analysis of the heart, rib and lung retention was assessed using a simple region of interest technique. Pulmonary function was evaluation by the means of whole-body plethysmography, diffusing capacity of the lung for carbon monoxide, forced oscillation technique and cardiopulmonary exercise testing.
RESULTS
Pulmonary tracer uptake estimated by lung to rib retention ratio was higher in ATTRv amyloidosis patients compared with control subjects: median 0.62 (0.55-0.69) vs 0.51 (0.46-0.60); p = 0.014. Analysis of relation between lung Tc-HMDP retention and pulmonary function parameters shown statistically significant correlations with total lung volume (% predicted), lung reactance (X 5 Hz) and peak VO, suggesting total lung capacity restriction impaired elastic properties of the lung and poor aerobic capacity.
CONCLUSION
Our study suggests that some grade of pulmonary retention of Tc-HMDP may occur in patients with cardiac ATTRv amyloidosis, which can elicit deleterious effects on patient's lung function and aerobic capacity.
Topics: Amyloidosis; Humans; Lung; Prealbumin; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate
PubMed: 35346209
DOI: 10.1186/s12931-022-01995-x -
Pediatric Research Jun 2022Children with Down syndrome are at risk for significant pulmonary co-morbidities, including recurrent respiratory infections, dysphagia, obstructive sleep apnea, and...
BACKGROUND
Children with Down syndrome are at risk for significant pulmonary co-morbidities, including recurrent respiratory infections, dysphagia, obstructive sleep apnea, and pulmonary vascular disease. Because the gold standard metric of lung function, spirometry, may not be feasible in children with intellectual disabilities, we sought to assess the feasibility of both airwave oscillometry and spirometry in children with Down syndrome.
METHODS
Thirty-four children with Down syndrome aged 5-17 years were recruited. Participants performed airwave oscillometry and spirometry before and 10 min after albuterol. Outcomes include success rates, airway resistance and reactance pre- and post-bronchodilator, and bronchodilator response.
RESULTS
Participants were median age 9.2 years (interquartile range 7.2, 12.0) and 47% male. Airwave oscillometry was successful in 26 participants (76.5%) and 4 (11.8%) were successful with spirometry. No abnormalities in airway resistance were detected, and 16/26 (61.5%) had decreased reactance. A positive bronchodilator response by oscillometry was observed in 5/23 (21.7%) of those with successful pre- and post-bronchodilator testing.
CONCLUSIONS
Measures of pulmonary function were successfully obtained using airwave oscillometry in children with Down syndrome, which supports its use in this high-risk population.
IMPACT
Children with Down syndrome are at risk for significant pulmonary co-morbidities, but the gold standard metric of lung function, spirometry, may not be feasible in children with intellectual disabilities. This may limit the population's enrollment in clinical trials and in standardized clinical care. In this prospective study of lung function in children with Down syndrome, airwave oscillometry was successful in 76% of participants but spirometry was successful in only 12%. This study reinforces that measures of pulmonary function can be obtained successfully using airwave oscillometry in children with Down syndrome, which supports its use in this high-risk population.
Topics: Asthma; Bronchodilator Agents; Child; Down Syndrome; Female; Humans; Intellectual Disability; Lung; Male; Oscillometry; Prospective Studies; Spirometry
PubMed: 34326475
DOI: 10.1038/s41390-021-01664-7 -
Sarcoidosis, Vasculitis, and Diffuse... 2021Sarcoidosis is a systemic inflammatory granulomatous disease which commonly affects intrathoracic lymph nodes, lung parenchyma and airways.
BACKGROUND
Sarcoidosis is a systemic inflammatory granulomatous disease which commonly affects intrathoracic lymph nodes, lung parenchyma and airways.
OBJECTIVES
To measure respiratory impedance using Impulse Oscillometry (IOS) in patients with pulmonary sarcoidosis and compare the parameters with healthy controls.
METHODS
Patients diagnosed with sarcoidosis (n=28); and age and gender matched healthy controls (n=17) were recruited. Lung volumes and capacities were measured by spirometry and respiratory system impedance was assessed using Impulse Oscillometry System (IOS). Measurements were performed before and 15 minutes after inhalation of a short acting bronchodilator. The IOS and spirometric parameters were compared between two groups and correlated. ROC curve analysis was also performed to identify the IOS parameters which can discriminate between sarcoidosis and healthy controls.
RESULTS
Resistance at 5 and 20 Hz (R5 and R20), small airway resistance (R5-R20), resonant frequency (F) and area of reactance (AX) were significantly higher in Sarcoidosis subjects compared with controls. Reactance at 5 and 20 Hz (X5 and X20) were significantly lower in sarcoidosis. FEV (% predicted) and FVC (% predicted) were significantly lower in patients with sarcoidosis while FEV/FVC ratio and peak expiratory flow rate (PEF) values were comparable. Post bronchodilator inhalation, there was improvement in airway resistance and reactance, but no significant changes observed in spirometric parameters. R5, X5 and R5-R20 are promising parameters to discriminate sarcoidosis from healthy controls.
CONCLUSION
Increased airway resistance is a better indicator of airway involvement than airflow limitation by spirometry in pulmonary sarcoidosis.
PubMed: 34744428
DOI: 10.36141/svdld.v38i3.8674 -
American Journal of Respiratory and... Feb 2024Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early...
Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early pathological impairments during tidal breathing. This study evaluates the prevalence and association of abnormal oscillometry parameters with respiratory symptoms and respiratory diseases in a general adult population. A total of 7,560 subjects in the Austrian LEAD (Lung, hEart, sociAl, boDy) Study with oscillometry measurements (computed with the Resmon Pro FULL; Restech Srl) were included in this study. The presence of respiratory symptoms and doctor-diagnosed respiratory diseases was assessed using an interview-based questionnaire. Rrs and Xrs at 5 Hz, their inspiratory and expiratory components, the area above the Xrs curve, and the presence of tidal expiratory flow limitation were analyzed. Normality ranges for oscillometry parameters were defined. The overall prevalence of abnormal oscillometry parameters was 20%. The incidence of abnormal oscillometry increased in the presence of symptoms or diagnoses: 17% (16-18%) versus 27% (25-29%), < 0.0001. All abnormal oscillometry parameters except Rrs at 5 Hz were significantly associated with respiratory symptoms/diseases. Significant associations were found, even in subjects with normal spirometry, with abnormal oscillometry incidence rates increasing by 6% (4-8%; < 0.0001) in subjects with symptoms or diagnoses. Abnormal oscillometry parameters are present in one-fifth of this adult population and are significantly associated with respiratory symptoms and disease. Our findings underscore the potential of oscillometry as a tool for detecting and evaluating respiratory impairments, even in individuals with normal spirometry.
Topics: Adult; Humans; Oscillometry; Lung; Respiration; Exhalation; Respiratory Tract Diseases; Spirometry; Forced Expiratory Volume; Airway Resistance
PubMed: 37972230
DOI: 10.1164/rccm.202306-0975OC