Patients with non-cystic fibrosis bronchiectasis who visited the outpatient clinic of Respiratory Medicine at a university-affiliated tertiary hospital during two calendar years were consecutively and prospectively included in this study. The healthy control group included staff members, interns, graduate students, and people without respiratory symtoms who underwent health check-ups and had a normal chest CT scan..
The diagnosis of bronchiectasis was based on the presentation of typical clinical symptoms (chronic cough, purulent sputum and repeated haemoptysis), signs of localised or persistent moist rales on pulmonary auscultation, and one of the following findings on high-resolution computed tomography (HRCT): (1) bronchial wall thickening and an enlarged lumen, where the ratio of the bronchus diameter to that of the accompanying artery is 1:1; (2) irregular cystic dilation with a gas-fluid level.
The exclusion criteria were as follows: (1) acute exacerbation within the past four weeks, defined as increased amount of sputum, aggravated cough or shortness of breath, haemoptysis, fever (body temperature >37.3°C), new onset of moist rales, or new infectious lesion on chest CT; (2) presence of allergic diseases (including but not limited to asthma, allergic rhinitis, allergic purpura, and urticaria), diffuse pan-bronchiolitis, allergic bronchopulmonary aspergillosis (ABPA), Kartagener syndrome, pneumoconiosis, or a history of lung resection and chest wall surgery; (3) presence of malignant tumours, severe cardiac dysfunction, chronic renal failure, or neuromuscular system diseases.
The study was approved by our hospital’s Ethics Committee. All patients provided written informed consent to participate in the present study.
Plethysmography, spirometry, and IOS were performed according to the European Respiratory Society (ERS) and the American Thoracic Society (ATS) lung function test guidelines. All subjects were offered an opportunity to familiarise themselves with the testing equipment by watching a video and demonstration by technicians and also undergoing a pilot test within 5 days prior to the actual test. The pilot test results were not documented. Patients who used inhalation medication were instructed to discontinue the medication for at least 24 hours before the test. On the day of the actual pulmonary function test, reversibility was tested using 400 µg of salbutamol, and the parameters were measured before and after salbutamol administration. The non-force-dependent parameters obtained by IOS were measured first, then the slow lung capacity (SVC) and finally, the force-dependent parameters.
Plethysmography and spirometry
The MasterScreen (CareFusion Co, California, US) instrument was used for plethysmography and spirometry. Plethysmography was performed to determine the following lung function parameters: residual volume (RV), total lung capacity (TLC) and RV/TLC ratio. Spirometry was used to determine the following parameters: the vital capacity (VC), forced vital capacity (FVC), forced vital capacity in one second (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF), maximal expiratory flow (MEF) at 75% of the VC (MEF75), MEF at 50% of the VC (MEF50), MEF at 25% of the VC (MEF25), and maximal mid-expiratory flow (MMEF75/25). The baseline lung function level was expressed as the percentage of the predicted value (% pred). Pulmonary function tests were performed in strict accordance with the latest ATS/ERS guidelines.
Impulse oscillometry (IOS)
The SentrySuite® IOS system (CareFusion Co, California, US) with SentrySuite® software was used for IOS measurement. The system was calibrated each day before the measurement. The following parameters were collected: central resistance (Rc), peripheral resistance (Rp), total respiratory impedance (Z5), resistance at 5 Hz (R5), resistance at 10 Hz (R10), resistance at 15 Hz (R15), resistance at 20 Hz (R20), resistance at 25 Hz (R25), resistance at 35 Hz (R35), reactance at 5 Hz (X5), and resonant frequency (Fres). The difference between R5–R20, which was an indicator of small airway obstruction, was also calculated.,
Definition of bronchodilatation (BDT) positive
The patients were divided into two subgroups based on their BDT results; a positive and a negative BDT cohort, and subgroup analyses were performed. According to the ATS/ ERS definition, a significant bronchodilator response, i.e. positive BDT was defined as an improvement of ≥ 12% and ≥ 200mL in either FEV1 or FVC after inhalation of bronchodilator compared to before..
Bronchiectasis severity stratification
A number of scoring systems were adopted to stratify the severity of bronchiectasis, including the Bhalla, BRICS, modified Reiff, Bronchiectasis Severity Index (BSI), and FACED scores. Bhalla score involves nine CT features, and is calculated by subtracting the CT scores from 25, yielding a score that ranges from 3 to 25 (mild 16 to 25; moderate 9 to 15, severe 3 to 8 points). BRICS is a simplified radiological score based on two components: bronchial enlargement and number of bronchopulmonary segments with emphysema. The BRICS scoreranges from 0 to 5 (mild 1pt; moderate 2 to 3 pts, severe >3 pts). The modified Reiff scores involves the evaluation of the severity of the enlargement of airways by comparing the diameter of the airway with the diameter of the adjacent pulmonary artery, and points are awarded for each lobe (1 = < 2 times, 2 =2-3 times, 3 = >3 times the diameter of the adjacent pulmonary artery). Since the lingula is treated as a separate lobe, the maximum score is 18 points (mild 0 to 6; moderate 7 to 12, severe 13 to 18 points).
The Bhalla, BRICS and modified Reiff scores are mainly based on the radiological changes of bronchiectasis. The BSI and FACED scores on the other hand incorporate clinical variables with radiological changes to predict clinical outcomes of bronchiectasis. The BSI score incorporates HRCT scores, age, FEV1, dyspnoea, body mass index, exacerbations, hospital admissions and colonisation with either Pseudomonas aeruginosa or other pathogenic organisms, to produce a score that ranges from 0 to 26 (mild 0 to 4; moderate 5 to 8; severe ≥9 points). Finally, the FACED score incorperates five variables: the FEV1, age, colonisation of Pseudomonas, lobe engagement and dyspnoea scores, to produce a score that ranges from 0 to 7 (mild 0 to 2; moderate 3 to 4, severe 5 to 8 points).
We also listed individual parameter such as lobe engagement, type of enlargement, the predominant feature of bronchial wall thickening and enlargement, mucus plugs, atelectasis or lung consolidation, the number of segments with emphysema, as well as the number of bullae.
Categorical variables were presented as frequencies or percentages, and compared using the Chi-square test (or Fisher’s exact test when appropriate). Depending on the distribution, continuous variables were presented as means and standard deviations (SD) when data was normally distributed or as medians with interquartile ranges (IQR) then the distribution was not normal. Comparison between two groups was performed by the Student’s t-test if the data was normally distributed or Mann–Whitney U-test when the distribution as not normal. The normality of the distribution was tested using the Shapiro-Wilk test. The Kruskal–Wallis test or one-way ANOVA test were used to compare IOS parameters and lung function among patients presenting with different severities of bronchiectasis stratified by the FACED, BSI, modified Reiff, Bhalla and BRICS scores. Spearman’s rank correlation coefficient was used for bivariate correlation analysis between IOS parameters, spirometric parameters and broncheistasis severity scores. IOS parameters that significantly differed between the BDT positive and negative cohorts were then used to predict airway reversibilityReceiver operating characteristic (ROC) curves were performed, and the area under the curve (AUC) of the different IOS parameters was comparedusing DeLong test. Wilcoxon matched-pairs signed-rank test was used for comparison the IOS parameter before and after bronchodilatation. For all analyses, p-values <0.05 were considered statistically significant. All statistical analyses were performed using Stata version 15.1(StataCorp; Texas; USA).