Background Clinical and research utility of non-cardiac ultrasound (US) in chronic obstructive pulmonary disease (COPD) has been widely investigated. However, there is no systematic review assessing the clinical values of non-cardiac US techniques in COPD. Methods We systematically searched electronic databases from inception to 24 June 2020. Two independent reviewers in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines extracted data. A narrative synthesis of the results was conducted considering non-cardiac US techniques that looked for diaphragm, muscles and bones in patients with COPD. Results In total, 2573 abstracts were screened, and 94 full-text papers were reviewed. A total of 54 studies met the inclusion criteria. Thirty-five studies assessed the diaphragm, while 19 studies evaluated different muscles, including limb muscles and pulmonary lesions in COPD using US. Of the 54 included studies, 30% (16/54) evaluated the changes in either limb muscles or diaphragmatic features before and after physical interventions; 67% (36/54) assessed the correlations between sonographic features and COPD severity. Indeed, 14/15 and 9/13 studies reported a significant reduction in diaphragm excursion and thickness in COPD compared with healthy subjects, respectively; this was correlated significantly with the severity and prognosis of COPD. Three studies reported links between diaphragm length and COPD, where lower diaphragm length correlated with poorer prognosis and outcomes. Quadriceps (rectus femoris), ankle dorsiflexor (tibialis anterior) and vastus lateralis were the most common muscles in COPD assessed by US. More than 70% (12/17) of the studies reported a significant reduction in the cross-sectional area (CSA) of the rectus femoris, rectus femoris and vastus lateralis thickness in COPD compared with healthy subjects. Quadriceps CSA and thickness correlated positively with COPD prognosis, in which patients with reduced quadriceps CSA and thickness have higher risk of exacerbation, readmission and death. Conclusion US measurements of diaphragm excursion and thickness, as well as lower limb muscles strength, size and thickness, may provide a safe, portable and effective alternative to radiation-based techniques in diagnosis and prognosis as well as tracking improvement postintervention in patients with COPD.

Background: Bronchodilator responsiveness (BDR) is commonly used in the diagnosis of lung disease. Although small airways dysfunction is a feature of asthma and COPD, physiological tests of small airways are not included in guidelines for BDR testing. This systematic review assessed the current evidence of BDR using small airways function in asthma and COPD. Methods: The systematic review used standard methodology with the protocol prospectively registered on PROSPERO (CRD42020164140). Electronic medical databases (EMBASE and Medline) were searched using related keywords. Abstracts and full texts were screened independently by two reviewers. Studies that reported the change of physiological small airways function and FEV₁ were included in the review. The revised Cochrane risk of bias tool for RCT and NIH quality assessment tool for cohort and cross-sectional studies were used to evaluate the studies. Results: A total of 934 articles were identified, with 12 meeting the inclusion criteria. Ten studies included asthma patients, 1 study included COPD patients and 1 study included both asthma and COPD. A total of 1104 participants were included, of whom 941 were asthmatic, 64 had COPD and 109 were healthy controls. Studies were heterogeneous in design including the device, dose and time intervals for BDR assessment. A small airway BDR was seen for most tests in asthma and COPD, including oscillometry (R5-20, reactance (X5), area of reactance (AX) and resonant frequency (Fres)) and Maximal Mid Expiratory Flow. Conclusion: There is a measurable BDR in the small airways. However, with no consensus on how to assess BDR, studies were heterogeneous. Further research is needed to inform how BDR should be assessed, its clinical impact and place in routine clinical practice.

Background Asthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use spirometric measures for asthma assessment. This systematic review aimed to assess whether the most commonly reported tests of small airways function could contribute to the diagnosis of asthma. Methods Standard systematic review methodology was used, and a range of electronic databases was searched (Embase, MEDLINE, CINAHL, CENTRAL, Web of Science, DARE). Studies that included physiological tests of small airways function to diagnose asthma in adults were included, with no restrictions on language or date. The risk of bias and quality assessment tools used were Agency for Healthcare Research and Quality tool for cross-sectional studies and Quality Assessment of Diagnostic Accuracy Studies 2 for diagnostic test accuracy (DTA) studies. Results 7072 studies were identified and 10 studies met review criteria. 7 included oscillation techniques and 5 included maximal mid-expiratory flow (MMEF). Studies were small and of variable quality. In oscillometry, total resistance (R5) and reactance at 5 Hz (X5) was altered in asthma compared with healthy controls. The percentage predicted of MMEF was lower in patients with asthma compared with controls in all studies and lower than the % predicted forced expiratory volume in 1 s. In DTA of oscillometry, R5 showed a sensitivity between 69% and 72% and specificity between 61% and 86%. Conclusion There were differences in the results of physiological tests of small airway function in patients with asthma compared with controls. However, studies are small and heterogeneous. Further studies are needed to assess the effectiveness of these tests on a larger scale, including studies to determine which test methodology is the most useful in asthma.

Background: Chronic obstructive pulmonary disease (COPD) is diagnosed and its severity graded by traditional spirometric parameters (forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) and FEV₁, respectively) but these parameters are considered insensitive for identifying early pathology. Measures of small airway function, including forced expiratory flow between 25% and 75% of vital capacity (FEF_25-75), may be more valuable in the earliest phases of COPD. This study aimed to determine the prevalence of low FEF_25-75 in ever-smokers with and without airflow limitation (AL) and to determine whether FEF_25-75 relates to AL severity. Method: A retrospective analysis of lung function data of 1458 ever-smokers suspected clinically of having COPD. Low FEF_25-75 was defined by z-score<−0.8345 and AL was defined by FEV₁/FVC z-scores<−1.645. The severity of AL was evaluated using FEV₁ z-scores. Participants were placed into three groups: normal FEF_25-75/ no AL (normal FEF_25-75/AL−); low FEF_25-75/ no AL (low FEF_25-75/AL−) and low FEF_25-75/ AL (low FEF_25-75/AL+). Results: Low FEF_25-75 was present in 99.9% of patients with AL, and 50% of those without AL. Patients in the low FEF_25-75/AL− group had lower spirometric measures (including FEV₁ FEF_25-75/FVC and FEV₃/FVC) than those in the normal FEF_25-75/AL− group. FEF_25-75 decreased with AL severity. A logistic regression model demonstrated that in the absence of AL, the presence of low FEF_25-75 was associated with lower FEV₁ and FEV₁/FVC even when smoking history was accounted for. Conclusions: Low FEF_25-75 is a physiological trait in patients with conventional spirometric AL and likely reflects early evidence of impairment in the small airways when spirometry is within the ‘normal range’. FEF_25-75 likely identifies a group of patients with early evidence of pathological lung damage who warrant careful monitoring and reinforced early intervention to abrogate further lung injury.

Chronic obstructive pulmonary disease (COPD) is common and debilitating. Most patients with COPD experience intermittent, acute deterioration in symptoms which require additional therapy, termed exacerbations. Exacerbations are prevalent in COPD and are associated with poor clinical outcomes including death, a faster decline in lung health, and a reduced quality of life. Current guidelines highlight the need to treat exacerbations promptly and then mitigate future risk. However, exacerbations are self-reported, difficult to diagnose and are treated with pharmacological therapies which have largely been unchanged over 30 years. Recent research has highlighted how exacerbations vary in their underlying cause, with specific bacteria, viruses, and cell types implicated. This variation offers the opportunity for new targeted therapies, but to develop these new therapies requires sensitive tools to reliably identify the cause, the start, and end of an exacerbation and assess the response to treatment. Currently, COPD is diagnosed and monitored using spirometric measures, principally the forced expiratory volume in 1 s and forced vital capacity, but these tests alone cannot reliably diagnose an exacerbation. Measures of small airways' function appear to be an early marker of COPD, and some studies have suggested that these tests might also provide physiological biomarkers for exacerbations. In this review, we will discuss how exacerbations of COPD are currently defined, stratified, monitored, and treated and review the current literature to determine if tests of small airways' function might improve diagnostic accuracy or the assessment of response to treatment.

The small airways comprise the largest cross-sectional area of the lungs, however, assessing and reporting abnormalities for this region of the bronchial tree has been practically and scientifically uncertain. Using routinely collected spirometry data for patients with either asthma or COPD, the accuracy of % predicted values for defining small airways dysfunction was assessed. A z-score of ≤ −1.645 of the maximal-mid expiratory flow (MMEF) was used as the gold standard for defining abnormality in the small airways. Records of 3396 patients were included in the analysis. The false positive (FP) rates were 24.6 %, 16.1 %, 11.5 %, or 7.9 % when the % predicted value of 80 %, 70 %, 65 %, or 60 % were used, respectively. Sex, age, and BMI were associated with FP rates. Males were more likely to be categorised as FP with odds ratio (OR) between 1.10 and 1.49 across % predicted groups. Age was associated with FP rates with an OR between 1.01 and 1.08. The BMI was also associated with FP rates with an OR of 1.03 across all % predicted groups. Assessing the association of age groups with FP rate showed that those above 60 years old were more likely to be categorised as FP with an OR between 1.23 and 73.2 compared to those less than 30 years old. When assessing the small airways in clinical practice or for scientific purposes, the % predicted values overestimate the actual impairment leading to FP interpretation. Utilising z-score values are recommended to assess the small airways using the spirometric index, MMEF.