Small Airway Dysfunction In Patients Research Articles

Oscillometry-Defined Small Airway Dysfunction in Patients with Chronic Obstructive Pulmonary Disease.

The prevalence of small airway dysfunction (SAD) in patients with chronic obstructive pulmonary disease (COPD) across different ethnicities is poorly understood. This study aimed to estimate the prevalence of SAD in stable COPD patients. We conducted a cross-sectional study of 196 consecutive stable COPD patients. We measured pre- and post-bronchodilator (BD) lung function and respiratory impedance. The severity of COPD and lung function abnormalities was graded in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SAD was defined as either difference in whole-breath resistance at 5 and 19 Hz > upper limit of normal or respiratory system reactance at 5 Hz < lower limit of normal. The cohort consisted of 95.9% men, with an average age of 66.3 years. The mean forced expiratory volume 1 second (FEV1) % predicted was 56.4%. The median COPD assessment test (CAT) scores were 14. The prevalence of post-BD SAD across the GOLD grades 1 to 4 was 14.3%, 51.1%, 91%, and 100%, respectively. The post-BD SAD and expiratory flow limitation at tidal breath (EFLT) were present in 62.8% (95% confidence interval [CI], 56.1 to 69.9) and 28.1% (95% CI, 21.9 to 34.2), respectively. COPD patients with SAD had higher CAT scores (15.5 vs. 12.8, p<0.01); poor lung function (FEV1% predicted 46.6% vs. 72.8%, p<0.01); lower diffusion capacity for CO (4.8 mmol/min/kPa vs. 5.6 mmol/min/kPa, p<0.01); hyperinflation (ratio of residual volume to total lung capacity % predicted: 159.7% vs. 129%, p<0.01), and shorter 6-minute walk distance (367.5 m vs. 390 m, p=0.02). SAD is present across all severities of COPD. The prevalence of SAD increases with disease severity. SAD is associated with poor lung function and higher symptom burden. Severe SAD is indicated by the presence of EFLT.

Evaluation of small airway dysfunction in patients with pneumoconiosis, a cross-sectional study

Objective: Pneumoconiosis is an irreversible, progressive parenchymal lung disease caused by inhalation of mineral dust. Inhaled particles in the working environment can cause inflammation and fibrosis in the lung, affecting all respiratory tracts, including the large and small airways. Our study aimed to evaluate the frequency and risk factors of small airway dysfunction (SAD) in patients diagnosed with pneumoconiosis. Methods: The study population consisted of 331 patients diagnosed with pneumoconiosis between 01/01/2018 and 31/05/2023. Pneumoconiosis was diagnosed with a history of occupational inorganic dust exposure, radiologic findings compatible with pneumoconiosis, and exclusion of other diagnoses. Two readers evaluated the chest radiographs of the patients according to the International Classification of Pneumoconiosis Radiographs of the International Labor Organization. SAD was defined as at least two FEF50, FEF75, and FEF25-75 measurements below 65% of their predicted values. Results: SAD was found in 47.7% of the patients. There was a statistically significant difference between age and the prevalence of SAD, but there was no statistically significant difference between smoking status and the prevalence of SAD. It was observed that 41.9% of the patients with pneumoconiosis who had never smoked had SAD. As the cigarette pack-years increased, the incidence of SAD increased. SAD was presented 38.7% in Stage 1, 50.7% in Stage 2, and 57.6% in Stage 3 pneumoconiosis cases. SAD was seen in 35.1% of pneumoconiosis cases without PMF. In pneumoconiosis patients with PMF, the frequency of SAD increased with increasing opacity size. Conclusion: It was found that the frequency of SAD increased as the stage of pneumoconiosis increased. In patients with pneumoconiosis, SAD was observed in both smokers and never smokers, independent of large airway obstruction. Therefore, early small airway dysfunction should be considered when monitoring the health of patients with pneumoconiosis.

Дисфункція дрібних дихальних шляхів та можливості її корекції при астмі

Abstract. Background. Although randomized controlled trials have shown that asthma control is an achievable goal, real-life studies over the past 20 years have shown that asthma remains poorly controlled in a significant proportion of patients, even among those receiving treatment at asthma specialist, and in patients with mild asthma who regularly take inhaled corticosteroids. Even when asthma control is achieved, it is not optimal on all GINA steps. The small airways have been recognized as the primary site of airflow limitation in asthma. The aim of the work: to study, according to the literature, the peculiarities of the dysfunction of the small airways in asthma and to evaluate the possibilities of its treatment. Materials and methods. Scientific articles that covered the pathophysiology of small airways disorders, their impact on asthma control, diagnostic methods, and pharmacological treatment methods were analyzed. The results. Airways with an internal diameter < 2 mm, which do not contain cartilage in their walls and extend from the 8th generation of the airways to the periphery of the lung, are collectively called “small airways”. They are called the QUIET ZONE because they are difficult to assess and treat in patients with asthma who are not optimally controlled but have relatively normal FEV1 and disproportionate small airways dysfunction (SAD). Predominant in patients at all stages of treatment, associated with poor disease control. The ATLANTIS study showed that up to 91 % of patients with asthma have. The small airways have a high density of corticosteroid and β2-adrenoceptors, which means that they can be influenced. The main task is that the drugs should reach these small airways. Conventional inhalers that generate particles larger than 2 μm do not address the problem of SAD in patients with asthma. Inhaler devices that produce ultrafine particles of inhaled corticosteroids alone or in combination with long-acting β-agonists with a diameter of less than 2 μm have the potential to improve long-term asthma control along with a corresponding improvement in small airway function. The fixed combination of beclomethasone dipropionate with formoterol has optimal deposition in the respiratory tract — central pulmonary deposition accounts for 66 %, and peripheral — 34 % of the dose, thus the drug is delivered to both the central and peripheral respiratory tracts and affects inflammation and bronchoconstriction throughout the lungs. This is facilitated by MODULITE technology. The effectiveness and safety of the use of the BDP/F combination (Foster) in MART regimen is confirmed by a significant evidence base, which guaranteed its place in the Track1 treatment of asthma. Conclusions: Patients with asthma have a serious inflammatory process in the peripheral airways, which makes them the main site of obstruction in asthma; SAD predominates in patients at all stages of asthma, is associated with poor disease control, is responsible for air trapping, correlates with poor asthma control1, and predicts an increased risk of exacerbations in patients. The fixed combination of beclamethasone/formoterol in one inhaler (Foster) is the only extrafinely dispersed fixed combination of ICS/LABA that reaches the small airways; the fixed combination of BDP/Formoterol in the MART regimen provides a significant reduction in the frequency of severe complications, hospitalizations, emergency calls, and reduces the number of courses of systemic corticosteroids.

The value of concentration of alveolar nitric oxide in diagnosing small airway dysfunction in patients with stable asthma.

Exhaled nitric oxide (FeNO) is a simple, noninvasive, and reproducible test, and FeNO (50 ml/s) is often used to reflect airway inflammation. The peripheral small airway/alveolar nitric oxide (NO) concentration is derived from the output of NO at multiple flow rates. Concentration of alveolar NO (CANO), which has been reported to reflect peripheral small airway inflammation, may be related to parameters that reflect abnormal small airway function. This study aims to investigate the relationship among CANO levels, clinical features, and small airway function-related indicators in patients with stable asthma and to provide a simple method for monitoring small airway function in asthma. We recruited 144 patients with well-controlled, stable asthma, including 69 patients with normal small airway function (normal group) and 75 patients with small airway dysfunction (abnormal group). CANO and pulmonary function were measured. CANO was significantly higher in the abnormal group ([7.28 ± 3.25]ppb) than the normal group CANO ([2.87 ± 1.50]ppb). FEF25-75%pred ([55.0 ± 16.5]%), FEF50%pred ([46.4 ± 13.2]%), and FEF75%pred ([41.9 ± 13.1]%) in abnormal group were significantly lower compared with normal group ([89.9 ± 7.5]%), ([80.9 ± 6.8]%), and ([73.8 ± 5.0]%). CANO was negatively correlated and FEF25-75%pred, FEF50%pred, and FEF75%pred (r = -0.87, P < 0.001; r = -0.82, P < 0.001; r = -0.78, P < 0.001). CANO was positively correlated with age (r = 0.27, P = 0.001). The area under the ROC curve was 0.875 for CANO. The optimal cutoff point of 5.3ppb had sensitivity and specificity values of 72% and 92% in diagnosing small airway dysfunction. CANO has diagnostic value for small airway dysfunction, and the optimal cutoff value is 5.3ppb. However, the diagnostic evidence is still insufficient, so it still needs further exploration for its value in detecting small airway dysfunction.

Small airways dysfunction in patients with systemic sclerosis and interstitial lung disease.

A number of studies report small airways involvement in patients with systemic sclerosis (SSc). Furthermore, small airways dysfunction is increasingly recognized in patients with interstitial lung disease (ILD) of idiopathic or autoimmune etiology. The objectives of this study were to evaluate small airways function in SSc patients with ILD and explore the effect of treatment on small airways function by using conventional and contemporary pulmonary function tests (PFTs). This single-center, prospective, observational study included a total of 35 SSc patients, with and without ILD based on HRCT scan, evaluated by a special radiologist blindly. Clinical data were collected from all patients who were also assessed for HRCT findings of small airways disease. Small airways function was assessed by classic spirometry, measurement of diffusing capacity for carbon monoxide, body plethysmography, single breath nitrogen washout (N2SBW) and impulse oscillometry (IOS). The prevalence of small airways dysfunction according to R5-R20, phase III slopeN2SBW and CV/VC methodologies was calculated in the total SSc population. Pulmonary function tests were compared between: (a) SSc-ILD and non-ILD patients and (b) two time points (baseline and follow up visit) in a subset of SSc-ILD patients who received treatment for ILD and were re-evaluated at a follow up visit after 12 months. Phase III slopeN2SBW and R5-R20 showed the highest diagnostic performance for detecting small airways dysfunction among SSc patients (61 and 37.5%, respectively). Twenty three SSc patients were found with ILD and 14 of them had a 12-month follow up visit. SSc-ILD patients compared to those without ILD exhibited increased phase III slopeN2SBW ≥120% (p = 0.04), R5-R20 ≥0.07 kPa/L/s (p = 0.025), airway resistance (Raw) (p = 0.011), and special airway resistance (sRaw) (p = 0.02), and decreased specific airway conductance (sGaw) (p = 0.022), suggesting impaired small airways function in the SSc-ILD group. Radiographic features of SAD on HRCT were observed in 22% of SSc-ILD patients and in none of SSc-non-ILD patients. Comparison of PFTs between baseline and follow-up visit after 12 months in the 14 SSc-ILD treated patients, showed improvement of phase III slopeN2SBW (p = 0.034), R5-R20 (p = 0.035) and Raw (p = 0.044) but not sRaw and sGaw parameters. Phase III slopeN2SBW and R5-R20 may reveal small airways dysfunction in SSc associated ILD before structural damage and may be partially improved in a subset of patients receiving treatment for ILD.

Investigation of small airway function of occupational asthma at different stages

Objective: To analyze the characteristics of small airway dysfunction in patients with occupational asthma, and explore the significance of small airway function indicators in the evaluation of occupational asthma. Methods: A total of 53 patients with occupational asthma diagnosed in our hospital from December 2008 to December 2018 were retrospectively collected in May 2020. 55 healthy people were included as the control group (NC group) and 58 bronchial asthma patients as BA group. The general information and baseline pulmonary function (FVC、FEV(1)、PEF) of the subjects were collected, the pulmonary function were reexamined and small airway function (FEF(25%)pred、FEF(50%)pred、FEF(75%)pred、MMEF(25-75%)pred) were tested at the time of diagnosis and remission. Results: There was no significant difference in pulmonary function and asthma control score (ACT) between OA group and BA group (P=0.356, 0.610, 0.364, 0.430, 0.533, 0.759, 0.426, 0.632) . The incidence of small airway dysfunction in OA group was 77.4%. The indexes of small airway function (FEF(25%)pred, FEF(50%)pred, FEF(75%)pred, MMEF(25-75%)pred) were lower than those in the NC group (P<0.001) . The small airway function indexes of mild and moderate OA patients in remission stage were improved (P=0.029, 0.182) , but the abnormal rate of small airway function was still 62.3%, and there was no significant difference compared with those at the time of diagnosis (P=0.091) . Small airway function (MMEF(25-75%)pred, FEF(50%)pred) was correlated with large airway function (FEV(1)% pred, PEF% pred) (P=0.001) . Conclusion: Small airway dysfunction often occurs and persists in patients with occupational asthma, and has a certain correlation with large airway function indexes.

Small airway dysfunction in Chinese patients with idiopathic pulmonary fibrosis

BackgroundRecent years, idiopathic pulmonary fibrosis (IPF) is thought to be a disease of alveoli as well as small airways. This study aimed to demonstrate the clinical feature, predictor, and prognosis of small airway dysfunction (SAD) in Chinese patients with IPF.MethodsWe enrolled 416 patients with IPF who hospitalized in Beijing Chao-Yang Hospital from 2000 to 2014 in this study, and the follow-up ended at December 2016. We collected demographic information, clinical examination results, spirometry results, HRCT results, and blood gas results during the study. Logistic regression analysis was used to identify the predictor for SAD. The COX proportional hazard model was used to analysis the prognosis effect of SAD.ResultsAmong all the participants, 165 (39.66%) patients had SAD. FEV1 (% predicted) and FEV3/FVC were significantly associated with SAD in patients with IPF. IPF patients with lower FEV1 (% predicted, OR 30.04, 95% CI 9.61–93.90) and FEV3/FVC (OR 77.76, 95% CI 15.44–391.63) had increased risk for SAD. Patients with SAD were associated with significantly increased risk of mortality in patients with IPF (HR 1.73, 95% CI 1.02–2.92), as well as in IPF patients without other pulmonary comorbidities (COPD, emphysema, and asthma).ConclusionsSpirometry-defined SAD was like 40% in patients with IPF. Lower FEV1 (% predicted) and FEV3/FVC were main predictors for SAD. IPF patients with SAD showed poorer prognosis.

Association of Airway Eosinophilia with Small Airway Dysfunction in Patients with Mild and at Risk for COPD.

Association of Airway Eosinophilia with Small Airway Dysfunction in Patients with Mild and at Risk for COPD.

Small-Airway Dysfunction is Involved in the Pathogenesis of Asthma: Evidence from Two Mouse Models.

BackgroundThere has been growing evidence of small-airway dysfunction in patients with asthma. Few studies have evaluated the mechanism of small-airway dysfunction in mouse models of asthma.PurposeWe explored the correlation between small-airway spirometric variables and large-airway function or inflammation in different endotypes of asthma.MethodsOvalbumin (OVA) sensitization/challenge was used to produce a type 2 (T2)-high asthma model, and OVA combined with ozone exposure (OVA + ozone) was used for the T2-low asthma model with increased neutrophils. Spirometry, airway responsiveness, cytokine levels in bronchoalveolar lavage fluid (BALF), and pathological analyses of lung slices stained with hematoxylin-eosin, periodic acid–Schiff, and Masson’s trichrome stain were all determined. Muc5ac expression in lung tissue was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR), and alpha-smooth muscle actin was measured by immunohistochemistry.ResultsInflammatory cells infiltrated the lung tissue and inflammatory cytokines were increased in the BALF of both the OVA and OVA + ozone groups, compared with the control group. Peribronchial hypersecretion and collagen deposition were evident in the models. The OVA + ozone group showed greater neutrophilic infiltration and peribronchial smooth muscle proliferation than the OVA group. Large-airway obstruction, small-airway dysfunction, and airway hyperresponsiveness were confirmed in both models. Small-airway functional variables, such as MMEF (mean midexpiratory flow, average flow from 25 to 75% forced vital capacity [FVC]) and FEF50 (forced expiratory flow at 50% of FVC), were positively correlated with large-airway function and had a stronger negative correlation with airway inflammation, mucus secretion, and responsiveness than large-airway function.ConclusionSmall-airway dysfunction was evident in the two endotypes of asthma and was correlated with severe airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The small airways may be an important target in asthma treatment, and further research in the role of small-airway variables in the pathogenesis of asthma is warranted.

Small airway dysfunction in patients with cough variant asthma: a retrospective cohort study

BackgroundCough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness (BHR) and airway inflammatory subtypes between CVA and classic asthma (CA), and investigate the relationship between these markers to determine the accuracy as indicators of CVA.MethodsA total of 825 asthmatic patients participated in the study and 614 were included. 614 patients underwent spirometry and a bronchial challenge with methacholine and 459 patients performed induction sputum cell test.ResultsThe number of CVA patients showed less small airway dysfunction than those of CA patients (p < 0.005). The degree of small airways dysfunction was higher in the CA group compared with the CVA group (p < 0.001). Small airways dysfunction was severer in the eosinophilic airway inflammatory subtype compared with other subtypes (p < 0.05).The area under curve of MMEF, FEF50 and FEF75 (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD20 and 4.7% of sputum eosinophils was the best diagnostic value for CVA with an AUC of 0.582 and 0.575 (p = 0.001 and p = 0.005, respectively).ConclusionsThe eosinophilic airway inflammatory subtype may be increased small airway dysfunction. The value of small airways, BHR and induction sputum cells in CVA prediction, which reflected significant, but not enough to be clinically useful.

Diagnosis of small airway dysfunction in patients with chronic obstructive pulmonary disease

Background: Small airway dysfunction (SAD) is a functional hallmark of chronic obstructive pulmonary disease (COPD). However, SAD prevalence and its role in COPD pathophysiology are not yet sufficiently studied.Background: Small airway dysfunction (SAD) is a functional hallmark of chronic obstructive pulmonary disease (COPD). However, SAD prevalence and its role in COPD pathophysiology are not yet sufficiently studied.Aim: To assess the prevalence of SAD in COPD patients by various functional diagnostic methods, such as spirometry, body plethysmography, and impulse oscillometry (IOS).Materials and methods: This was an cross-sectional study. Spirometry, body plethysmography and IOS were used in 132 COPD patients in remission under standard anti-COPD treatments. The presence of SAD was confirmed by at least one of the following criteria or their combination: 1) by spirometry: the difference between vital capacity (VC) and forced vital capacity (FVC) &gt; 10%; 2) the presence of air trapping by body plethysmography; 3) identification of the frequency dependence of the resistive resistance at 5 to 20 Hz (R5 - R20 &gt; 0.07 kPa x s/l), as assessed by IOS.Results: Mean forced expiratory volume in 1 s (FEV1) was 42.9% of predicted. Depending on the severity of the obstruction, the patients were divided into 4 groups: 7 patients (group 1) had the obstruction corresponding to GOLD 1 stage, 37 (group 2) to GOLD 2, 49 (group 3) to GOLD 3, and 39 (group 4) to GOLD 4. SAD was found in 96% of COPD patients, whereas in those with severe obstruction (GOLD 3-4), it was present in 100% of the cases. By spirometry, SAD was identified only in 67% of COPD patients, by body plethysmography in 75% of COPD patients (in those with severe obstruction (GOLD 3 and 4) in 88 and 97%, respectively). With IOS, it was possible to identify SAD in 94% of patients and in 100% of those with severe obstruction (GOLD 3-4).Conclusion: With deterioration of obstructive pulmonary ventilation abnormalities in COPD patients, there is a progressive increase in small airway dysfunction. Impulse oscillometry seems to be the most effective method for diagnosis of small airway dysfunction, as it helped to identify SAD in 94% of COPD patients and in 100% of those with severe and very severe obstruction.

Kūno pletizmografijos rodiklių pokyčiai po bronchų dilatacinio mėginio

Įvadas. Smulkieji kvėpavimo takai dėl specifinių anatominių ir fiziologinių savitumų paprastai nesukelia akivaizdžių spirometrinių rodiklių pokyčių. Todėl, norint vertinti ir smulkiųjų kvėpavimo takų būklę bei jų atsaką į skiriamą gydymą, tikslinga atlikti išsamesnį plaučių funkcijos įvertinimą. Tyrimo tikslas. Įvertinti kūno pletizmografijos rodiklių pokyčius pobronchų dilatacinio mėginio pacientams, sergantiems lėtinėmis obstrukcinėmis plaučių ligomis, ir palyginti su spirometriniais rodikliais. Tyrimo metodika. Atliktas prospektyvinis tyrimas, kuriame dalyvavo lėtine obstrukcine plaučių liga (LOPL) (n=21) ir astma (n=21) sergantys asmenys. Kiekvienam tiriamajam buvo atlikta spirometrija ir kūno pletizmografija prieš ir praėjus 20 min. po 400 µg salbutamolio įkvėpimo. Pagal bronchų dilatacinio mėginio rezultatus (ΔFEV1≥12 proc. ir ≥200 ml, palyginus su pradine verte) tiriamieji suskirstyti į dvi grupes: teigiamo ir neigiamo dilatacinio mėginio. Rezultatai. Iš viso ištirti 42 vidutinio amžiaus (59,8±2,1 m.) asmenys. Teigiamas dilatacinis mėginys nustatytas 12 tiriamųjų (28,6 proc.), neigiamas – 30 (71,4 proc.). Abiejose tyrimo grupėse po salbutamolio įkvėpimo reikšmingai sumažėjo sRaw, padidėjo sGaw, tačiau FRC, RV, RV/TLC kito tik teigiamo dilatacinio mėginio grupėje. Nustatytos statistiškai reikšmingos sąsajos abiejose grupėse tarp FEV1 ir sRaw, RV/TLC prieš ir po dilatacinio mėginio. Abiejose grupėse nustatyta reikšminga sąsaja tarp FEV1 ir RV verčių prieš dilatacinį mėginį. Išvados. Kūno pletizmografija suteikia išsamesnės informacijos, palyginus su spirometrija, apie kvėpavimo takų, ypač smulkiųjų, funkcinius sutrikimus sergantiesiems obstrukcinėmis plaučių ligomis.

Possibilities of pulse oscillometry in the diagnosis of small airway dysfunction in patients with bronchial asthma

Small airway dysfunction (SAD) is associated with poorly controlled asthma and frequent exacerbations. Objective: To assess the prevalence of SAD in asthmatics using spirometry, body plethysmography, and impulse oscillometry (IOS). Materials and methods: The observational cross-sectional study of 61 patients with asthma was performed. Conclusion available SAD was made on the basis of identifying one of the criteria or their combination: 1) slow vital capacity (SVC) - forced vital capacity (FVC) &gt;10% according spirometry; 2) "air trapping" according body plethysmography; 3) presence of pathological frequency dependence of the resistance (R) at 5 and 20 Hz (R5-R20 &gt; 0,07 kPa•sec/l) according IOS. Results: The analysis was performed for the entire group as well as for patients with FEV1 &gt; 80 %pred. and FEV1/SVC &lt; 0,7 (group 1) and patients with FEV1 &gt; 80 %pred. and normal FEV1/SVC (group 2). SAD was most often diagnosed using IOS and the selected criterion R5-R20&gt;0,07 kPa •sec/l since 75% of patients had this deviation in the entire group, 65% of patients in group 1 and 55% of patients in group 2 whereas only in 48% and 24% of cases in the entire group according body plethysmography and spirometry, respectively. Conclusion: SAD is definitely observed in patients with asthma. IOS is a more effective method of diagnosing SAD compared to spirometry and body plethysmography and can serve as a supplement functional method, especially in cases of normal parameters of spirometry and body plethysmography in asthmatics.

Increased prevalence of small airways dysfunction in patients with systemic sclerosis as determined by impulse oscillometry.

The prevalence and clinical implications of small airways involvement in SSc are still to be fully elucidated. The goal of the present work is to assess the prevalence of small airways dysfunction by impulse oscillometry and to determine whether it correlates with selected disease-related features and respiratory-related quality of life. Ninety-four SSc patients and 93 healthy controls were studied by impulse oscillometry measurements. Small airways dysfunction was defined as the difference between resistance at low frequency, i.e. 5 Hz, and resistance at high frequency, i.e. 20 Hz, termed 'R5-R20', ⩾0.07 kPa/l/s. The St George's Respiratory Questionnaire was used to measure health impairment in SSc patients. Radiological features of small airways disease and parenchymal abnormalities on high resolution CT chest scans were jointly assessed by two thoracic radiologists. Small airways dysfunction was present in 21.5% of the SSc patient cohort, with a prevalence almost 5-fold higher compared with controls, and it was significantly associated with worse respiratory-related quality of life. Radiological features consistent with small airways abnormalities were detected in 25% of SSc patients, mostly in the absence of interstitial lung changes. Combining functional and radiological evaluations, one-third of the SSc cohort showed at least one feature of small airways involvement, which was associated with the lcSSc phenotype and with longer disease duration. The current study strengthens the hypothesis that small airway dysfunction might be a feature of SSc-related lung involvement, providing the first data on its significant impact on respiratory-related quality of life. A full assessment of lung function in SSc patients should include impulse oscillometry as a complementary technique, due to potential clinical and therapeutic implications.

Small Airway Dysfunction by Impulse Oscillometry in Symptomatic Patients with Preserved Pulmonary Function

Asthma and chronic obstructive pulmonary disease are characterized by persistent airway inflammation and airflow limitation. Early detection of these diseases in patients with respiratory symptoms and preserved pulmonary function (PPF) defined by spirometry is difficult. Impulse oscillometry (IOS) may have better sensitivity than effort-dependent forced expiratory flow between 25% and 75% (FEF25%-75%) to detect small airway dysfunction (SAD). To identify SAD in patients with respiratory symptoms and PPF using IOS. Medical records of symptomatic patients without acute or known structural lung diseases were evaluated. Patients had bronchodilator testing and IOS in the outpatient clinic between March 1 and July 31, 2017. Correlations between respiratory symptoms, spirometry, and IOS parameters were determined. Among 349 patients enrolled to the study, 255 (73.1%) patients met the criteria of PPF. The IOS parameters-difference in resistance at 5 Hz and resistance at 20 Hz , reactance at 5 Hz, resonant frequency (Fres), and area under reactance curve between 5 Hz and resonant frequency-were significantly correlated with FEF25%-75%. The cutoffs for SAD were difference in resistance at 5 Hz and resistance at 20 Hz greater than 0.07 kPa/(L/s), reactance at 5 Hz less than-0.12 kPa/(L/s), Fres greater than 14.14 Hz, and area under reactance curve between 5 Hz and resonant frequency greater than 0.44 kPa/L. Of the IOS parameters, Fres and reactance at 5 Hz had the highest sensitivity and specificity. When compared with FEF25%-75%, Fres had greater sensitivity to detect SAD in patients with PPF. Patients with IOS-defined SAD had a significantly higher incidence of wheeze or sputum production than did those defined by FEF25%-75%. Patients with respiratory symptoms and PPFmay have SAD, which can be identified with the aid of IOSin addition to spirometry.

Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study

Small airways dysfunction (SAD) is well recognised in asthma, yet its role in the severity and control of asthma is unclear. This study aimed to assess which combination of biomarkers, physiological tests, and imaging markers best measure the presence and extent of SAD in patients with asthma. In this baseline assessment of a multinational prospective cohort study (the Assessment of Small Airways Involvement in Asthma [ATLANTIS] study), we recruited participants with and without asthma (defined as Global Initiative for Asthma severity stages 1-5) from general practices, the databases of chest physicians, and advertisements at 29 centres across nine countries (Brazil, China, Germany, Italy, Spain, the Netherlands, the UK, the USA, and Canada). All participants were aged 18-65 years, and participants with asthma had received a clinical diagnosis of asthma more than 6 months ago that had been confirmed by a chest physician. This diagnosis required support by objective evidence at baseline or during the past 5 years, which could be: positive airway hyperresponsiveness to methacholine, positive reversibility (a change in FEV1 ≥12% and ≥200 mL within 30 min) after treatment with 400 μg of salbutamol in a metered-dose inhaler with or without a spacer, variability in peak expiratory flow of more than 20% (measured over 7 days), or documented reversibility after a cycle (eg, 4 weeks) of maintenance anti-asthma treatment. The inclusion criteria also required that patients had stable asthma on any previous regular asthma treatment (including so-called rescue β2-agonists alone) at a stable dose for more than 8 weeks before baseline and had smoked for a maximum of 10 pack-years in their lifetime. Control group participants were recruited by advertisements; these participants were aged 18-65 years, had no respiratory symptoms compatible with asthma or chronic obstructive pulmonary disease, normal spirometry, and normal airways responsiveness, and had smoked for a maximum of 10 pack-years. We assessed all participants with spirometry, body plethysmography, impulse oscillometry, multiple breath nitrogen washout, CT (in selected participants), and questionnaires about asthma control, asthma-related quality of life (both in participants with asthma only), and health status. We applied structural equation modelling in participants with asthma to assess the contribution of all physiological and CT variables to SAD, from which we defined clinical SAD and CT SAD scores. We then classified patients with asthma into SAD groups with model-based clustering, and we compared asthma severity, control, and health-care use during the past year by SAD score and by SAD group. This trial is registered with ClinicalTrials.gov, number NCT02123667. Between June 30, 2014, and March 3, 2017, we recruited and evaluated 773 participants with asthma and 99 control participants. All physiological measures contributed to the clinical SAD model with the structural equation modelling analysis. The prevalence of SAD in asthma was dependent on the measure used; we found the lowest prevalence of SAD associated with acinar airway ventilation heterogeneity (Sacin), an outcome determined by multiple breath nitrogen washout that reflects ventilation heterogeneity in the most peripheral, pre-acinar or acinar airways. Impulse oscillometry and spirometry results, which were used to assess dysfunction of small-sized to mid-sized airways, contributed most to the clinical SAD score and differed between the two SAD groups. Participants in clinical SAD group 1 (n=452) had milder SAD than group 2 and comparable multiple breath nitrogen washout Sacin to control participants. Participants in clinical SAD group 2 (n=312) had abnormal physiological SAD results relative to group 1, particularly their impulse oscillometry and spirometry measurements, and group 2 participants also had more severe asthma (with regard to asthma control, treatments, exacerbations, and quality of life) than group 1. Clinical SAD scores were higher (indicating more severe SAD) in group 2 than group 1, and we found that these scores were related to asthma control, severity, and exacerbations. We found no correlation between clinical SAD and CT SAD scores. SAD is a complex and silent signature of asthma that is likely to be directly or indirectly captured by combinations of physiological tests, such as spirometry, body plethysmography, impulse oscillometry, and multiple breath nitrogen washout. SAD is present across patients with all severities of asthma, but it is particularly prevalent in severe disease. The clinical classification of SAD into two groups (a milder and a more severe group) by use of impulse oscillometry and spirometry, which are easy to use, is meaningful given its association with GINA severity stages, asthma control, quality of life, and exacerbations. Chiesi Farmaceutici SpA.

Unlocking the quiet zone: the small airway asthma phenotype

The small airways in the distal lung have been called the quiet zone because they are difficult to assess and treat in patients with asthma who have disproportionate impairment of small airway function. Evidence is accumulating to support a distinct clinical phenotype for patients with asthma who have impaired small airway function. The small airway asthma phenotype, which is prevalent in patients at all steps of management guidelines, seems to be associated with poor disease control. Alternatively, small airway dysfunction might be a sensitive indicator of early disease rather than a phenotype. Conventional coarse-particle inhalers, which emit particles larger than 2 μm, might not address persistent small airway dysfunction in patients with asthma. To target the entire lung with extra-fine particle formulations (smaller than 2 μm) of inhaled corticosteroids alone or in combination with long-acting β-agonists might result in improved long-term asthma control along with a commensurate improvement in small airway function. Prospective randomised controlled trials with extra-fine-particle inhaled drugs are now needed for patients with the small airway asthma phenotype.

Small airways dysfunction in patients with AIDS and Pneumocystis carinii pneumonia.

Abnormalities of small airways function may have clinical relevance in AIDS patients with Pneumocystis carinii pneumonia (PCP) since obstructive dysfunction at alveolar levels may impede delivery of aerosolized medication. This study was designed to determine if small airways dysfunction is present in AIDS patients with PCP despite normal standard spirometric results. Ten AIDS patients with documented PCP and no other identifiable pulmonary infection without respiratory failure and with a normal FEV1/FVC ratio were evaluated. Small airways function was assessed by the FEF75 and the change in maximum expiratory flow while breathing a helium-oxygen mixture compared to room air (delta Vmax50%) with and without bronchodilator administration. Testing was done before and after completion of intravenous therapy for PCP. Despite absence of cough or wheezing at the time of evaluation and a normal FEV1/FVC ratio, significant obstructive dysfunction of the small airways was demonstrated in 6 of 10 patients, which improved with bronchodilators. Three weeks of intravenous therapy for PCP had no effect on these abnormalities. The degree of small airways dysfunction was greater than could be explained by smoking history alone. Small airways dysfunction, which can be improved with bronchodilator administration, may be present in AIDS patients with PCP despite normal spirometry and absence of cough or wheezing. Screening for small airways dysfunction may identify patients who might benefit from bronchodilator administration prior to inhalation of aerosolized medications.