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The European Respiratory Journal Mar 2023Small airways dysfunction (SAD) in asthma is difficult to measure and a gold standard is lacking. The aim of this study was to develop a simple tool including items of...
BACKGROUND
Small airways dysfunction (SAD) in asthma is difficult to measure and a gold standard is lacking. The aim of this study was to develop a simple tool including items of the Small Airways Dysfunction Tool (SADT) questionnaire, basic patient characteristics and respiratory tests available depending on the clinical setting to predict SAD in asthma.
METHODS
This study was based on the data of the multinational ATLANTIS (Assessment of Small Airways Involvement in Asthma) study including the earlier developed SADT questionnaire. Key SADT items together with clinical information were now used to build logistic regression models to predict SAD group (less likely or more likely to have SAD). Diagnostic ability of the models was expressed as area under the receiver operating characteristic curve (AUC) and positive likelihood ratio (LR+).
RESULTS
SADT item 8, "I sometimes wheeze when I am sitting or lying quietly", and the patient characteristics age, age at asthma diagnosis and body mass index could reasonably well detect SAD (AUC 0.74, LR+ 2.3). The diagnostic ability increased by adding spirometry (percentage predicted forced expiratory volume in 1 s: AUC 0.87, LR+ 5.0) and oscillometry (resistance difference between 5 and 20 Hz and reactance area: AUC 0.96, LR+ 12.8).
CONCLUSIONS
If access to respiratory tests is limited ( primary care in many countries), patients with SAD could reasonably well be identified by asking about wheezing at rest and a few patient characteristics. In (advanced) hospital settings patients with SAD could be identified with considerably higher accuracy using spirometry and oscillometry.
Topics: Humans; Asthma; Respiratory Function Tests; Spirometry; Forced Expiratory Volume; ROC Curve
PubMed: 36517179
DOI: 10.1183/13993003.00558-2022 -
BMJ Open Respiratory Research Sep 2022Asthma is a frequent respiratory condition whose pathophysiology relies on altered interactions between bronchial epithelium, smooth muscle cells (SMC) and immune... (Review)
Review
Asthma is a frequent respiratory condition whose pathophysiology relies on altered interactions between bronchial epithelium, smooth muscle cells (SMC) and immune responses. Those leads to classical hallmarks of asthma: airway hyper-responsiveness, bronchial remodelling and chronic inflammation. Airway smooth muscle biology and pathophysiological implication in asthma are now better understood. Precise deciphering of intracellular signalling pathways regulating smooth muscle contraction highlighted the critical roles played by small GTPases of Rho superfamily. Beyond contractile considerations, active involvement of airway smooth muscle in bronchial remodelling mechanisms is now established. Not only cytokines and growth factors, such as fibroblats growth factor or transforming growth factor-β, but also extracellular matrix composition have been demonstrated as potent phenotype modifiers for airway SMC. Although basic science knowledge has grown significantly, little of it has translated into improvement in asthma clinical practice. Evaluation of airway smooth muscle function is still limited to its contractile activity. Moreover, it relies on tools, such as spirometry, that give only an overall assessment and not a specific one. Interesting technics such as forced oscillometry or specific imagery (CT and MRI) give new perspectives to evaluate other aspects of airway muscle such as bronchial remodelling. Finally, except for the refinement of conventional bronchodilators, no new drug therapy directly targeting airway smooth muscle proved its efficacy. Bronchial thermoplasty is an innovative and efficient therapeutic strategy but is only restricted to a small proportion of severe asthmatic patients. New diagnostic and therapeutic strategies specifically oriented toward airway smooth muscle are needed to improve global asthma care.
Topics: Asthma; Bronchodilator Agents; Cytokines; Humans; Monomeric GTP-Binding Proteins; Myocytes, Smooth Muscle; Transforming Growth Factors
PubMed: 36109087
DOI: 10.1136/bmjresp-2022-001351 -
International Journal of Chronic... 2021The response to treatment and progression of Chronic Obstructive Pulmonary Disease (COPD) varies significantly. Small airways disease (SAD) is being increasingly... (Review)
Review
The response to treatment and progression of Chronic Obstructive Pulmonary Disease (COPD) varies significantly. Small airways disease (SAD) is being increasingly recognized as a key pathological feature of COPD. Studies have brought forward pathological evidence of small airway damage preceding the development of emphysema and the detection of obstruction using traditional spirometry. In recent years, there has been a renewed interest in the early detection of SAD and this has brought along an increased demand for physiological tests able to identify and quantify SAD. Early detection of SAD allows early targeted therapy and this suggests the potential for altering the course of disease. The aim of this article is to review the evidence available on the physiological testing of small airways. The first half will focus on the role of lung function tests such as maximum mid-expiratory flow, impulse oscillometry and lung clearance index in detecting and quantifying SAD. The role of Computed Tomography (CT) as a radiological biomarker will be discussed as well as the potential of recent CT analysis software to differentiate normal aging of the lungs to pathology. The evidence behind SAD biomarkers sourced from blood as well as biomarkers sourced from sputum and broncho-alveolar lavage (BAL) will be reviewed. This paper focuses on CC-16, sRAGE, PAI-1, MMP-9 and MMP-12.
Topics: Biomarkers; Humans; Lung; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Spirometry
PubMed: 33628018
DOI: 10.2147/COPD.S280157 -
Chest Apr 2023The purpose of this study was to investigate physiological phenotypes of asthma in obesity.
BACKGROUND
The purpose of this study was to investigate physiological phenotypes of asthma in obesity.
RESEARCH QUESTION
Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity?
STUDY DESIGN AND METHODS
Cross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry.
RESULTS
Participants had class III obesity (BMI, 46.7 ± 6.6 kg/m in control subjects and 47.2 ± 8.2 kg/m in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5 Hz measured by oscillometry increased by 45% ± 27% and area under the reactance curve (AX) by 268% ± 236% in response to 16 mg/mL methacholine; in people with asthma, resistance at 5 Hz measured by oscillometry increased by 52% ± 38% and AX by 361% ± 295% in response to provocation concentration producing a 20% fall in FEV dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4 cm HO/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7 cm HO/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group.
INTERPRETATION
Peripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry.
Topics: Female; Humans; Methacholine Chloride; Cross-Sectional Studies; Asthma; Respiratory System; Spirometry; Bronchial Provocation Tests; Obesity; Airway Resistance; Forced Expiratory Volume
PubMed: 36610669
DOI: 10.1016/j.chest.2022.12.030 -
Chest Dec 2020To reduce the spread of the severe acute respiratory syndrome coronavirus 2, many pulmonary function testing (PFT) laboratories have been closed or have significantly... (Review)
Review
To reduce the spread of the severe acute respiratory syndrome coronavirus 2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. Because these mitigation strategies may be necessary for the next 6 to 18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFT, which includes spirometry, lung volume, and diffusion capacity measurement, is essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions. Both traditional and innovative alternatives to conventional testing must now be explored. These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, and novel digital health tools such as smartphone microphone spirometers and mobile health technologies along with integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options comes important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the coronavirus disease 19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease. The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.
Topics: Asthma; Breath Tests; COVID-19; Chronic Disease; Cystic Fibrosis; Delivery of Health Care; Humans; Hypertension, Pulmonary; Inventions; Lung Diseases; Lung Diseases, Interstitial; Lung Volume Measurements; Machine Learning; Oscillometry; Peak Expiratory Flow Rate; Pulmonary Diffusing Capacity; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Self-Management; Smartphone; Spirometry
PubMed: 32652095
DOI: 10.1016/j.chest.2020.06.065 -
Therapeutics and Clinical Risk... 2020Over the past decades, impulse oscillometry (IOS) has gained ground in the battery of pulmonary function tests. Performing the test requires minimal cooperation of the... (Review)
Review
Over the past decades, impulse oscillometry (IOS) has gained ground in the battery of pulmonary function tests. Performing the test requires minimal cooperation of the patient; therefore, it is a useful tool, especially in evaluating lung mechanics in children, elderly patients, and those who cannot perform spirometry. Oscillometry has also been used in both clinical and research departments. Studies were published mainly in asthma regarding detection of bronchodilator response and the therapeutic response to different drugs. Furthermore, it has been shown to be a sensitive technique to evaluate disease control. Other studied diseases were COPD, interstitial lung diseases, small airway disease, impairment of lung function due to exposure to occupational hazards or smoking, central airways obstruction, cystic fibrosis, monitoring lung mechanics during mechanical ventilation and sleep, neuromuscular diseases, lung transplant, and graft function. The aim of this review is to present the utility of oscillometry on the previously mentioned clinical fields.
PubMed: 33273817
DOI: 10.2147/TCRM.S275920 -
Frontiers in Medicine 2023Small airways play a major role in the pathogenesis and prognosis of chronic obstructive pulmonary disease (COPD) and asthma. More data on small airway dysfunction (SAD)...
Comparative assessment of small airway dysfunction by impulse oscillometry and spirometry in chronic obstructive pulmonary disease and asthma with and without fixed airflow obstruction.
BACKGROUND
Small airways play a major role in the pathogenesis and prognosis of chronic obstructive pulmonary disease (COPD) and asthma. More data on small airway dysfunction (SAD) using spirometry and impulse oscillometry (IOS) in these populations are required. The objective of this study was to compare the two methods, spirometry and IOS, for SAD detection and its prevalence defined by spirometry and IOS in subjects with COPD and asthma with and without fixed airflow obstruction (FAO).
DESIGN
This is a cross-sectional study.
METHODS
Spirometric and IOS parameters were compared across four groups (COPD, asthma with FAO, asthma without FAO, and healthy subjects). SAD defined by spirometry and IOS criteria were compared.
RESULTS
A total of 262 subjects (67 COPD, 55 asthma with FAO, 101 asthma without FAO, and 39 healthy controls) were included. The prevalence of SAD defined by using IOS and spirometry criteria was significantly higher in patients with COPD (62.7 and 95.5%), asthma with FAO (63.6 and 98.2%), and asthma without FAO (38.6 and 19.8%) in comparison with healthy control (7.7 and 2.6%). IOS is more sensitive than spirometry in the detection of SAD in asthma without FAO (38.6% vs. 19.8%, = 0.003) However, in subjects with FAO (COPD and asthma with FAO), spirometry is more sensitive than IOS to detect SAD (95.5% vs. 62.7%, < 0.001 and 98.2% vs. 63.6%, < 0.001, respectively).
CONCLUSION
Small airway dysfunction was significantly detected in COPD and asthma with and without FAO. Although IOS shows more sensitivity than spirometry in the detection of SAD in asthma without FAO, spirometry is more sensitive than IOS in patients with FAO including COPD and asthma with FAO.
PubMed: 37265488
DOI: 10.3389/fmed.2023.1181188 -
Biochemical Society Transactions Oct 2020Parkinson's disease (PD) is the second most common neurodegenerative disease. In recent years, it has been shown that leucine-rich repeat kinase 2 (LRRK2) has a crucial... (Review)
Review
Parkinson's disease (PD) is the second most common neurodegenerative disease. In recent years, it has been shown that leucine-rich repeat kinase 2 (LRRK2) has a crucial function in both familial and sporadic forms of PD. LRRK2 pathogenic mutations are thought to result in an increase in LRRK2 kinase activity. Thus, inhibiting LRRK2 kinase activity has become a main therapeutic target. Many compounds capable of inhibiting LRRK2 kinase activity with high selectivity and brain availability have been described. However, the safety of long-term use of these ATP-competitive LRRK2 kinase inhibitors has been challenged by several studies. Therefore, alternative ways of targeting LRRK2 activity will have a great benefit. In this review, we discuss the recent progress in the development of allosteric inhibitors of LRRK2, mainly via interfering with GTPase activity, and propose potential new intra and interprotein interactions targets that can lead to open doors toward new therapeutics.
Topics: Adenosine Triphosphate; Allosteric Site; Animals; Crystallography, X-Ray; Cytosol; Dimaprit; Dimerization; Enzyme Inhibitors; GTP Phosphohydrolases; GTP-Binding Proteins; Humans; Kinetics; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Microtubules; Mutation; Oscillometry; Parkinson Disease; Protein Conformation; Protein Domains; Protein Interaction Mapping; Protein Kinase Inhibitors; Single-Domain Antibodies; rab1 GTP-Binding Proteins
PubMed: 33079169
DOI: 10.1042/BST20200424 -
Wiener Klinische Wochenschrift May 2023After COVID-19 infection, persistent exercise intolerance, changes in lung function have been shown. Our aim is to investigate the correlation between impulse...
BACKGROUND
After COVID-19 infection, persistent exercise intolerance, changes in lung function have been shown. Our aim is to investigate the correlation between impulse oscillometry (IOS) parameters and exercise capacity by using incremental and endurance shuttle walk tests (ISWT, ESWT) and investigate the factors and parameters which might have an effect on both IOS parameters and exercise capacity tests.
METHOD
The patients who had a history of COVID-19 were enrolled into cross-sectional study according to inclusion criteria. The IOS parameters, ISWT, ESWT, smoking status, time since COVID-19 diagnosis, length of hospital stay, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), body mass index (BMI), fat-free mass index (FFMI), dyspnea, hospital anxiety-depression and fatigue severity scores were recorded.
RESULTS
The study comprised 72 patients, 71% of whom were male, with a mean age of 54 ± 10 years. After COVID-19 diagnosis, the median duration was 3 (min: 1, max: 5) months and 51 (71%) of the patients were hospitalized. The FEV1 and FVC values were in normal range. The area of reactance (AX), resonance frequency (Fres), reactance at 20 Hz (X20) and the difference between resonance at 20 and 5 Hz (R5-20) correlated with both ISWT and ESWT. The FEV1 correlated with all IOS parameters (p < 0.05). Reactance correlated with FFMI (p = 024, r = 0.267), different according to hospitalization (p = 0.02).
CONCLUSION
In COVID-19 survivors, there could be correlations between IOS parameters and exercise capacity; and between these parameters and FEV and FVC. Furthermore, small airway disease with normal spirometric functions could be related to decreased exercise capacity in COVID-19 survivors regardless of concomitant diseases, BMI, smoking status and time since COVID-19 diagnosis.
Topics: Humans; Male; Adult; Middle Aged; Female; Oscillometry; Cross-Sectional Studies; COVID-19 Testing; Exercise Tolerance; Spirometry; COVID-19
PubMed: 36583749
DOI: 10.1007/s00508-022-02137-5 -
American Journal of Respiratory and... Feb 2024
Topics: Humans; Oscillometry
PubMed: 38190700
DOI: 10.1164/rccm.202311-2127ED