Role of noninvasive methods for assessing stable non-cystic fibrosis bronchiectasis

doi:10.21203/rs.3.rs-23690/v1

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Role of noninvasive methods for assessing stable non-cystic fibrosis bronchiectasis

https://doi.org/10.21203/rs.3.rs-23690/v1

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Background: Bronchiectasis is characterized by the abnormal dilation of lung airways. Only some patients with bronchiectasis may clinically benefit from the treatment recommended in the guidelines of the European Respiratory Society. The value of noninvasive methods for assessing the clinical phenotypes of stable-state non-cystic ﬁbrosis (non-CF) bronchiectasis for treatable characteristics has not been adequately studied.

Methods: Eighty-nine patients with stable non-CF bronchiectasis were retrospectively enrolled. Patient characteristics, fractional exhaled nitric oxide (FeNO) values, and the results of blood tests for inflammatory markers, pulmonary function test, high-resolution computed tomography (HRCT), and bronchial hyper-responsiveness test or bronchodilator reversibility test were obtained. These data were used to assess the factors associated with the clinical phenotype of bronchiectasis.

Results: The majority of the patients were female (60.67%) and have an average age of 59.08±15.09 years old. The predicted percentages of forced expiratory volume in 1 s (FEV₁) and the ratio of FEV₁ and forced vital capacity were 56.17%±23.16% and 65.58%±15.26%, respectively. Eighteen (20.22%) of the patients with bronchiectasis had emphysema. The presence of emphysema in bronchiectasis was associated with a high airflow obstruction level. Seventeen (10.10%) of the patients with bronchiectasis had asthma. FeNO was signiﬁcantly higher in the group of patients with bronchiectasis and asthma than in the other two groups (p < 0.01). The erythrocyte sedimentation rate (ESR) of the bronchiectasis alone group was higher than those of the other two groups. Signiﬁcant negative correlations were found between ERS and FeNO levels (p = 0.02, r = −0.338), between HRCT score and FeNO levels (p = 0.04, r = −0.229), and between FEV₁ (% predicted) and HRCT scores (p = 0.0007, r = −0.3629). A signiﬁcant positive correlation was found between ERS and HRCT scores (p = 0.0001, r = 6326).

Conclusion: A remarkable proportion of patients with bronchiectasis have emphysema or asthma. Biomarkers, such as FeNO, and conventional lung function tests should be routinely used for phenotyping bronchiectasis for potential targeted therapy. ESR can be used as a biomarker to reflect the level of systemic inﬂammation and the severity of bronchiectasis. These approaches will provide a better understanding of patients with bronchiectasis and their clinical phenotypes and lead to a more individualized and effective therapy.

Pulmonology

bronchiectasis

fractional exhaled nitric oxide

asthma

emphysema

Bronchiectasis is characterized as a permanent enlargement of the airways secondary to chronic airway infections, airway inflammation, and structural damage [1].Bronchiectasis has multiple etiologies and a broad array of clinical presentations, such as daily cough, sputum expectoration, chronic infective syndrome, and periodic worsening of symptoms also known as exacerbations [2, 3]. The wide application of high-resolution computed tomography (HRCT) in clinical practice has led to the growing recognition that bronchiectasis is a common disease. Bronchiectasis has increased by 40% from 2004 to 2013 and is expected to increase to more than 3 million by 2020 [4, 5]. Despite the increasing prevalence of bronchiectasis, the regulatory authorities in the United States or Europe have not approved any medication for bronchiectasis except for bronchiectasis caused by cystic fibrosis (CF) [6, 7]. The European Respiratory Society guidelines for the management of bronchiectasis recommend this treatment⁷. However, only some patients with bronchiectasis may have clinical benefits from this treatment [8–11]. Therefore, we need to better assess the clinical phenotype of patients with bronchiectasis and look for a treatable trait for targeted therapy.

Bronchiectasis, as a chronic respiratory disease, is associated with mucus secretion, airway obstruction, chronic inflammation, and airway remodeling [12, 13]. Patients with bronchiectasis may manifest decreased lung function, increased systemic or airway inflammation, and HRCT abnormality [14, 15]. The elevation of systemic inflammatory markers, such as C-reactive protein (CRP) and total white blood cell count, is associated with disease severity [16]. As an inflammatory biomarker for the quantitative analysis of airway inflammation, fractional exhaled nitric oxide (FeNO) is effective in evaluating therapeutic response and clinical phenotype in patients with asthma and chronic obstructive pulmonary disease (COPD [17, 18]. However, the role of these non-invasive modalities in non-CF bronchiectasis has not been adequately studied.

Therefore, we aimed to assess the systemic and airway inflammations in patients with stable-state non-CF bronchiectasis and identify the associations among lung function, airway hyper-responsiveness, and/or airway reversibility with HRCT performance. We hope that these approaches will provide a better understanding of patients with bronchiectasis and their clinical phenotypes and lead to a more individualized and effective therapy.

Study subjects

Patients with stable bronchiectasis aged 18 years old or older admitted in the First Affiliated Hospital of Sun Yat-sen University from December 2017 to December 2019 were retrospectively enrolled in this study. The inclusion criteria were as follows. (1) The patient had bronchiectasis as confirmed by chest HRCT and remained exacerbation-free for at least 4 weeks [7]. (2) The patient underwent pulmonary function tests (PFTs), bronchodilator reversibility (BDR) test or bronchial hyper-responsiveness (BHR) test, and FeNO test without treatment of any oral or inhaled corticosteroid or bronchodilator within 72 h. (3) The patient must be a nonsmoker or an ex-smoker with smoking cessation of at least 6 months prior to FeNO tests. We excluded patients who were pregnant or lactating, had allergic bronchopulmonary aspergillosis, and had any evidence of exacerbation. CF is a rare disease in China. Thus, we postulated that all the enrolled patients have bronchiectasis that is not associated with CF.

The study was reviewed by the Institutional Research Ethics Committee of our hospital. This study did not gather the requirement for approval and informed consent, because it was not an intervening trial and was retrospective in nature.

Data Collection

The medical history, characteristics, and diagnostic data (FeNO values, blood tests, and PFT results) of the patients were obtained from their medical charts.

Hrct Scoring

We scored the HRCT scans of the patients with bronchiectasis according to the semi-quantitative scoring system suggested by Oikonomou [19]. This system is a “simplified” HRCT scoring system that includes three common parameters: “severity of bronchiectasis,” “severity of bronchial wall thickening,” and “atelectasis consolidation.” Each rating ranges from 0 to 3 (0 is none). Every involved lobe, including the left lingular lobe, was evaluated and scored according to this system. The final bronchiectasis severity was calculated as the total summation of the total involved lobes.

Feno Measurement

FeNO value was determined according to the recommendations of the American Thoracic Society by using a conventional chemiluminescence analyzer (NIOX MINO; Aerocrine AB, Sweden) [20]. The participants were instructed to use the online standardized single-breath technique, that is, inhale air without NO to total lung capacity (TLC) and complete the exhalation immediately into the device at a constant flow rate of 50 mL/s for 10 s. FeNO values more than 50 ppb have high probability for eosinophilic inflammation, values less than 25 ppb indicate a low probability, and values between 25 and 50 ppb signify intermediary probability.

PFT

Participants underwent PFT after the measurement of FeNO. PFT was performed using body plethysmography following the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test [21]. All participants performed PFT in a reproducible way, and the best values of each subject were selected.

Bhr Test

After baseline evaluation, the patients with a predicted percentage of forced expiratory volume in 1 s (FEV₁) of more than 70% should take the BHR test to rule out bronchial hyper-responsiveness. Airway hyper-responsiveness is expressed as the provocative concentration of histamine when FEV₁ decreased by 20% from the baseline (PC20). In our study, the positive response was defined as PC20 ≤ 8 mg/mL[21].

Bdr Test

The patients with FEV₁ (% predicted) of less than 70% should take the BDR test. The patients were subjected to spirometry test before and after receiving 400 µg inhalations of salbutamol with a spacer. A positive result was defined as the improvement of FEV₁ by more than 12% and an absolute increase of FEV₁ by more than 200 mL[21].

Statistical analysis

All data analyses were performed using SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA). The results are shown as mean ± standard deviation, number (%) of patients, or median (interquartile range) for quantitative variables or for non-normal variables when appropriate. The comparison of differences between groups was conducted by Student’s t-test for normally distributed variables or by Mann–Whitney U test for non-normally distributed variables. Categorical variables were compared using Chi-squared test. The relationship between FeNO levels and other variables, such as IgE, blood eosinophil count, blood eosinophil percentage, HRCT scores, and inflammatory marker level, was assessed by determining the Spearman’s rank correlation coefficients. P < 0.05 was defined as statistically significant. Statistical analyses and figures were performed in GraphPad Prism 5.

Study population

Eighty-nine patients with stable bronchiectasis were enrolled. The majority of the patients were female (60.67%) and had an average age of 59.08 ± 15.09 years old. Total WBC and eosinophil counts were 7.87 ± 3.15/mm³ and 202.23 ± 257.65 cells/µL, respectively. CRP level and erythrocyte sedimentation rate (ERS) were 14.17 ± 20.34 mg/L and 41.15 ± 20.34 mm/h, respectively. HRCT score was 14.27 ± 11.41. The other details of the patients with bronchiectasis are shown in Table 1.

Table 1

Baseline characteristics of study population
Parameter	Bronchiectasis (N = 89)
Mean age, years	59.08 ± 15.09
Sex (M:F), n	35:54
Height (cm)	160.42 ± 8.13
Weight (kg)	53.08 ± 10.54
Body surface area (m²)	1.53 ± 0.16
BMI (kg/m²)	20.61 ± 3.74 (range 11.67–29.38 )
WBC (× 10³/mm³)	7.87 ± 3.15
Total serum IgE (IU/mL)	131.36 ± 171.26
Blood eosinophil, absolute (cells/µL)	202.23 ± 257.65
Blood eosinophil percentage (%)	2.62 ± 2.35
CRP (mg/L)	14.17 ± 20.34
ESR (mm/h)	41.15 ± 20.34
HRCT score	14.27 ± 11.41
Note: Data are shown as mean ± standard deviation unless indicated otherwise. Abbreviations: M, male; F, female; BMI, body mass index; WBC: white blood cell; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; HRCT: high-resolution computed tomography.

Clinical Features And Pft Data Of Patients With Bronchiectasis

The mean FEV₁ (% predicted) was 56.17%±23.16%, and the mean ratio of FEV₁/forced vital capacity (FVC) was 65.58%±15.26%. This group of patients had a decreased diffusion capacity of the lung for carbon monoxide with an average percentage of 60.89%±18.53%. Sixty-seven patients had BDR test, and seven patients had an improvement of ≥ 12% in FEV₁ after treatment with 400 µg inhalations of salbutamol. Three among these patients had an absolute increase in FEV₁ of > 200 mL. Twenty-two patients had BHR test, and nine patients had positive response (PC20 ≤ 8 mg/mL). The average FeNO value was 20.34 ± 9.97 ppb.(Table 2)

Table 2

Clinical features and PFT data of patients with bronchiectasis
Parameter	Bronchiectasis (N = 89)
FVC (% predicted)	69.79 ± 20.32
FEV₁ (% predicted)	56.17 ± 23.16
FEV₁/FVC	65.58 ± 15.26
PEF (% predicted)	50.43 ± 23.56
MEF (% predicted)	39.06 ± 33.86
MEF25 (% predicted)	37.26 ± 42.82
MEF50 (% predicted)	35.0 ± 32.82
MEF75 (% predicted)	39.71 ± 27.03
MVV (% predicted)	61.71 ± 36.59
VC (% predicted)	67.48 ± 18.89
TLC (% predicted)	89.31 ± 19.33
RV (% predicted)	132.35 ± 43.21
RV/TLC (% predicted)	56.51 ± 12.63
DLCO (% predicted)	60.89 ± 18.53
BDR test	67
≥ 12% increase in FEV₁	7
≥ 12% + ≥200 mL in FEV₁	3
≥ 12% + ≥400 mL in FEV₁	0
BHR test Positive BHR test	22 9
FeNO (ppb)	21.74 ± 12.74
Notes: The measured pulmonary function values are presented as a predictive percentagData are shown as mean ± standard deviation unless indicated otherwise. Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; PEF, peak expiratory flow; MEF, maximal mid-expiratory flow; MEF25, forced expiratory flow after 25% of the FVC; MEF50, forced expiratory flow after 50% of the FVC; MEF75, forced expiratory flow after 75% of the FVC; MVV, maximal voluntary ventilation; VC, vital capacity; RV, residual volume; TLC, total lung capacity; DLCO, diffusion capacity of the lung for carbon monoxide; PFT, pulmonary function test; BDR, bronchodilator reversibility; BHR, bronchial hyper-responsiveness test; FeNO, fractional exhaled nitric oxide; ppb, parts per billion.

Clinical Features Of Patients In Different Subgroups Of Bronchiectasis

The subjects were divided into the bronchiectasis alone (60.67%), bronchiectasis with emphysema (20.22%), and bronchiectasis with asthma groups (19.10%) according to the HRCT scans, clinical data, pulmonary function data, and BHR or BDR test analytical data. Emphysema is defined as the diffused low-attenuation areas of the lung below the density threshold of − 950 Hounsfield unit[22]. Patients with only localized emphysema were excluded. The diagnosis of asthma was based on the combination of medical history and the criteria of the Global Initiative for Asthma (GINA[23]. No significant differences were observed with regard to age, gender, height, weight, body mass index, blood eosinophil count, and IgE level among these groups. The bronchiectasis alone group showed higher levels of systemic inflammatory markers, such as ESR, than the other two groups (P < 0.05). The presence of emphysema in bronchiectasis has been associated with a higher airflow obstruction as manifested by the lower FEV₁ (% predicted), FEV₁/FVC, peak expiratory volume (PEF, % predicted), and forced expiratory flow after 75% of the FVC (MEF75, % predicted) in the bronchiectasis with emphysema group than in the other two groups. The bronchiectasis with asthma group showed higher FeNO levels than the other two groups (P < 0.001). The detailed data of the patients in the three groups are listed in Table 3.

Table 3

Clinical features of patients in different subgroups of bronchiectasis
Parameter	Bronchiectasis alone (N = 54)	Emphysema (N =18)	Asthma (N = 17)	P value
Mean age (years)	58.17 ± 15.73	65.72 ± 13.57	54.94 ± 12.95	0.0802
Sex (M:F), n	17:37	11:7	7:10	0.088
Height (cm)	159.69 ± 8.96	161.17 ± 7.26	161.94 ± 6.02	0.557
Weight (kg)	51.37 ± 10.52	53.33 ± 9.21	58.24 ± 10.77	0.062
Body surface area (m²)	1.51 ± 0.17	1.55 ± 0.15	1.61 ± 0.15	0.138
BMI (kg/m²)	20.14 ± 3.81	20.49 ± 3.07	22.21 ± 3.93	0.083
FVC (% predicted)	68.31 ± 21.02	66.56 ± 15.48	77.88 ± 21.52	0.180
FEV₁ (% predicted)	57.44 ± 22.57	45.22 ± 22.10	63.71 ± 23.29	0.048
FEV₁/FVC	68.74 ± 15.32	55.78 ± 15.27	65.94 ± 10.66	0.006
PEF (% predicted)	52.80 ± 24.70	36.06 ± 12.81	58.12 ± 23.28	0.009
MEF (% predicted)	43.93 ± 39.04	26.11 ± 20.69	37.29 ± 23.02	0.150
MEF25 (% predicted)	44.61 ± 51.77	20.39 ± 15.64	31.76 ± 20.28	0.096
MEF50 (% predicted)	39.39 ± 38.72	21.89 ± 17.90	35.12 ± 18.98	0.147
MEF75 (% predicted)	41.69 ± 27.84	24.11 ± 14.66	49.94 ± 28.69	0.011
MVV (% predicted)	63.41 ± 41.64	53.94 ± 29.64	64.53 ± 24.50	0.603
VC (% predicted)	66.15 ± 20.09	64.33 ± 13.00	75.06 ± 19.18	0.174
TLC (% predicted)	85.89 ± 19.96	98.13 ± 17.56	90.90 ± 15.53	0.088
RV (% predicted)	125.13 ± 42.19	152.19 ± 42.15	133.80 ± 43.63	0.589
RV/TLC (% predicted)	55.59 ± 12.01	61.50 ± 13.41	52.80 ± 13.19	0.166
DLCO (% predicted)	59.69 ± 16.81	57.75 ± 22.50	72.00 ± 17.26	0.436
WBC (× 103/mm³)	8.13 ± 3.56	8.21 ± 2.60	6.74 ± 1.99	0.283
Total serum IgE (IU/mL)	142.34 ± 185.69	97.09 ± 99.63	139.84 ± 234.17	0.798
Blood eosinophil, absolute (cells/µL)	172.34 ± 160.17	136.67 ± 108.47	250.00 ± 176.26	0.145
Blood eosinophil percentage (%)	2.49 ± 2.19	2.15 ± 1.76	3.66 ± 3.26	0.193
CRP (mg/L)	16.70 ± 23.71	8.19 ± 7.74	11.91 ± 15.79	0.371
ESR (mm/h)	49.64 ± 27.78	23.00 ± 21.89	30.10 ± 29.58	0.033
FeNO (ppb)	16.98 ± 8.35	23.78 ± 9.83	34.71 ± 17.31	< 0.001
HRCT score	15.02 ± 11.48	13.59 ± 10.85	12.36 ± 12.33	0.717
Notes: The measured pulmonary function values are presented as a predictive percentage. Data are shown as mean ± standard deviation unless indicated otherwise. Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; PEF, peak expiratory flow; MEF, maximal mid-expiratory flow; MEF25, forced expiratory flow after 25% of the FVC; MEF50, forced expiratory flow after 50% of the FVC; MEF75, forced expiratory flow after 75% of the FVC; MVV, maximal voluntary ventilation; VC, vital capacity; RV, residual volume; TLC, total lung capacity; DLCO, diffusion capacity of the lung for carbon monoxide; PFT, pulmonary function test; BDR, bronchodilator reversibility; BHR, bronchial hyper-responsiveness test; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; M, male; F, female; BMI, body mass index; WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

Comparison of HRCT scores among the three groups

The three groups had no significant difference in HRCT scores( Fig. 1).

Comparison of FeNO levels among the three groups

The FeNO levels among the three groups were significantly different (P < 0.05). The FeNO value of the bronchiectasis with asthma group was 34.71 ± 17.31 ppb, which was significantly higher than those of the other groups (P < 0.001, Fig. 2).

Correlation of FeNO with blood eosinophil, IgE, systemic inflammatory markers, PFT and HRCT score

Significant negative correlations were found between FeNO levels and ESR (p = 0.02, r = − 0.338; Fig. 3), between FeNO levels and HRCT scores (p = 0.04, r = − 0.229; Figs. 3F), and between FEV₁ (% predicted) and HRCT scores (p = 0.0007, r = − 0.3629; Fig. 3G). A significant positive correlation was found between ESR and HRCT scores (p = 0.0001, r = 6326; Fig. 3I). No significant correlation was demonstrated between FeNO levels and blood eosinophil, CRP, or IgE (Table 3, Figs. 3A–C, 3E, and 3H).

We performed a retrospective study of patients with bronchiectasis. All 89 patients underwent HRCT, PFT, BDR or BHR, and FeNO tests. Bronchiectasis severity was assessed using the simplified HRCT scoring system. FEV₁ (% predicted) and FEV₁/FVC were 56.17%±23.16% and 65.58%±15.26%, respectively. This condition means that a large proportion of patients with bronchiectasis demonstrated an obstructive functional impairment. The overall levels of FeNO in the bronchiectasis groups, except the bronchiectasis with asthma group, were lower than 25 ppb, which is the lowest cut-off value in the recent guidelin[20]. This finding means that non-eosinophilic inflammatory process could be related to the pathogenesis of bronchiectasis. Seven patients had an improvement of ≥ 12% in FEV₁ after treatment with 400 µg inhalations of salbutamol, and nine patients showed airway hyperactivity, which means that a certain proportion of the patients have asthma or asthmatic characteristics.

The general relationship among asthma, emphysema, and bronchiectasis remains unclear[24]. Increasing degrees of chronic airway obstruction followed by emphysema may be seen and labeled as COPD as bronchiectasis progresses. Eighteen (20.22%) patients with bronchiectasis had emphysema. The presence of emphysema in bronchiectasis was associated with a higher airflow obstruction level as manifested by the lower FEV₁ (% predicted), FEV₁/FVC, PEF (% predicted), and MEF75 (% predicted) in bronchiectasis with emphysema group compared with the other two groups. The genetic overlap between emphysema and bronchiectasis is associated with alpha-1 antitrypsin deficiency; the biomarker of alpha-1 antitrypsin level is associated with disease severity[25].The presence of emphysema in bronchiectasis may lead to more frequent exacerbations, decreased quality of life, and reduced survival[11]. The causal relationship between bronchiectasis and emphysema needs to be adequately evaluated in longitudinal studies.

Some patients with bronchiectasis may have eosinophilia, elevated IgE, and at least partially reversible airway obstruction or hyper-responsiveness, which suggest an asthmatic component [26]. Sixty-seven patients had BDR test, and seven patients had an improvement of ≥ 12% in FEV₁ after receiving 400 µg inhalations of salbutamol. Three of these patients had an absolute increase in FEV₁ of > 200 mL. Twenty-two patients had BHR test, and nine patients had a positive response. In our study, the diagnosis of asthma was based on a combination of medical history and GINA criteria. Seventeen patients with bronchiectasis had asthma. Among these 17 patients, three patients had true positive BDR reversibility (improvement of ≥ 12% in FEV₁ and an increase of > 200 mL), and nine patients had a positive BHR test. The other five patients with a history of asthma had severe airflow limitations and thus were not able to achieve a positive BDR result. We conclude that patients with bronchiectasis and asthma experienced airway remodeling after long-term treatment with dual or triple inhalation, and this remodeling resulted in decreased airway reversibility. Hence, reversibility is an important feature of asthma to some extent, but it is not the most important and only feature identifying asthma in patients with bronchiectasis. The prevalence of asthma was 19.10% in the patients with bronchiectasis in our study. A. Padilla-Galo et al reported a high prevalence of bronchiectasis in patients with uncontrolled asthma[26]. We need to focus on the high prevalence of asthma or asthma characteristics in patients with bronchiectasis. In our study, FeNO was significantly higher in the bronchiectasis with asthma group than in the other two groups (P < 0.01). FeNO is a sensitive, reproducible, and noninvasive marker for directly detecting eosinophilic airway inflammation[27]. Endotyping to guide therapy has attracted much attention in bronchiectasis management, and biomarkers may be useful in identifying patients with bronchiectasis who may benefit from directed anti-inflammatory treatment. Bronchiectasis with asthma or asthma features represent a treatable trait for targeted therapy.

In this study, we used a “simplified” HRCT scoring system to assess the disease severity of patients with bronchiectasis and found no statistically significant difference in the HRCT scores among the three groups. This finding indicates that the radiographic severity in clinical practice does not seem to be necessarily associated with the clinical phenotype of bronchiectasis[27]. In our study, a significant negative correlation was observed between HRCT score and FEV₁ (% predicted) (p = 0.0007, r = − 0.3629). FEV₁ (% predicted) is related to large-airway lesions and is an indicator of airway obstruction severity. The repeatability of CT is poor because of the radiation risk and cost effectiveness. Conventional lung function tests, such as FEV₁ (% predicted), which reflects airway obstruction, can be used as a convenient and rapid method to assess the severity of bronchiectasis during the follow-up period.

A significant negative correlation was found between HRCT scores and FeNO levels (p = 0.04, r = − 0.229). The overall levels of FeNO in the bronchiectasis groups were lower than 25 ppb except for the bronchiectasis with asthma group (34.71 ± 17.31 ppb). The level of FeNO in patients with bronchiectasis decreased with increasing HRCT score for disease severity. FeNO is associated with airway eosinophilic inflammation and is negatively correlated with neutrophilic count in the induced sputum in patients with non-CF bronchiectasis[28]. This finding indicates that bronchiectasis severity is associated with increased non-eosinophilic inflammation.

Bronchiectasis without asthma or asthmatic features may present different inflammatory patterns. In our study, the bronchiectasis alone group showed higher levels of systemic inflammatory markers (e.g., ESR), which suggest a higher level of systemic chronic inflammation, than the other two groups (p < 0.05). A significant positive correlation was found between ESR and HRCT scores (p = 0.0001, r = 0.6326), and a negative correlation was found between ESR and FeNO levels (p = 0.02, r = − 0.338). The elevation of systemic inflammatory markers was associated with disease severity. The results suggested that systemic inflammation in patients with bronchiectasis is related to disease severity. ESR can be an easy-to-use method and a useful marker for assessing disease severity in patients with bronchiectasis. No previous study has demonstrated a correlation between ESR and HRCT scores before.

This study has several limitations. First, the work was a retrospective, single-center study that involves a relatively small number of patients. Second, this study focused on the baseline characteristics of patients with bronchiectasis. Lastly, the results may have still been affected by other treatments, although the patients discontinued their treatments within 72 h prior to blood test, PFT, and FeNO test.

In conclusion, a remarkable proportion of patients with bronchiectasis have emphysema and asthma. Biomarkers (e.g., FeNO) and conventional lung function tests (e.g., FEV₁) should be routinely used for phenotyping bronchiectasis for potential targeted therapy. ESR can be used as a biomarker to reflect the level of systemic inﬂammation and bronchiectasis severity. Additional studies are required to elucidate the clinical importance of the role of ESR and FeNO in the assessment of treatment response and the progression of bronchiectasis after anti-inﬂammatory therapy.

FeNO: fractional exhaled nitric oxide; VC: vital capacity; TLC: total lung capacity ; DLCO: diffusion capacity of the lung for carbon monoxide; PFT: pulmonary function test; FEV1¹: forced expiratory volume in 1 s; FVC: forced vital capacity; PEF: peak expiratory flow; MEF: maximal midexpiratory flow; MEF25: forced expiratory flow after 25% of the FVC; MEF50: forced expiratory flow after 50% of the FVC; MEF75: forced expiratory flow after 75% of the FVC; MVV: maximal voluntary ventilation; RV: residual volume; ppb: parts per billion; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate.

Data availability statement: The datasets used and/or analysed during the current study are available from the corresponding author on request.

Acknowledgements: The study was funded by the Project of Department of Finance of Guangdong Province(20160907), Science and Technology Planning Project of Guangdong Province(201707010185), National Natural Science Foundation of China(81770024).

Author contributions: Conceptualization: Feng-jia Chen，Geng-peng Lin , Yu-biao Guo, Yi-feng Luo. Data curation: Feng-jia Chen，Geng-peng Lin , Hui Yi , Xin-yan Huang, Yang-li Liu, Can-mao Xie, Yu-biao Guo, Yi-feng Luo. Formal analysis: Feng-jia Chen，Geng-peng Lin , Yu-biao Guo, Yi-feng Luo. Investigation: Feng-jia Chen，Geng-peng Lin , Hui Yi , Xin-yan Huang, Yang-li Liu, Can-mao Xie, Yu-biao Guo, Yi-feng Luo. Funding acquisition: Can-mao Xie, Yu-biao Guo. Methodology: Feng-jia Chen，Geng-peng Lin , Hui Yi , Xin-yan Huang, Yang-li Liu, Yu-biao Guo, Yi-feng Luo. Project administration: Feng-jia Chen，Geng-peng Lin , Hui Yi , Xin-yan Huang, Yang-li Liu, Can-mao Xie, Yu-biao Guo, Yi-feng Luo .Supervision: Yi-feng Luo, Yu-biao Guo. Writing—original draft: Feng-jia Chen, Geng-peng Lin, Yi-feng Luo, Yu-biao Guo. Writing—review and editing: Feng-jia Chen，Geng-peng Lin , Hui Yi , Xin-yan Huang, Yang-li Liu, Can-mao Xie, Yu-biao Guo, Yi-feng Luo.

Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults, Eur Respir J 2015, 45:1446-1462
REID LM. Reduction in bronchial subdivision in bronchiectasis, Thorax 1950, 5:233-247
O'Leary CJ, Wilson CB, Hansell DM, Cole PJ, Wilson R, Jones PW. Relationship between psychological well-being and lung health status in patients with bronchiectasis, Respir Med 2002, 96:686-692
Quint JK, Millett ER, Joshi M, Navaratnam V, Thomas SL, Hurst JR, et al. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study, Eur Respir J 2016, 47:186-193
Polverino E, Cacheris W, Spencer C, Operschall E, O, Donnell AE. Global burden of non-cystic fibrosis bronchiectasis: A simple epidemiological analysis, Eur Respir J 2012, 40:P3983
Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity, Lancet 2018, 392:880-890
Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, Murris M, Cantón R, Torres A, Dimakou K, De Soyza A, Hill AT, Haworth CS, Vendrell M, Ringshausen FC, Subotic D, Wilson R, Vilaró J, Stallberg B, Welte T, Rohde G, Blasi F, Elborn S, Almagro M, Timothy A, Ruddy T, Tonia T, Rigau D, Chalmers JD: European Respiratory Society guidelines for the management of adult bronchiectasis, Eur Respir J 2017, 50:
Nadig TR, Flume PA. Aerosolized Antibiotics for Patients with Bronchiectasis, Am J Respir Crit Care Med 2016, 193:808-810
De Soyza A, Aksamit T, Bandel TJ, Criollo M, Elborn JS, Operschall E, et al. a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis, Eur Respir J 2018, 51:
Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease, Lancet 2008, 372:1107-1119
Martinez-Garcia MA, Miravitlles M. Bronchiectasis in COPD patients: more than a comorbidity? Int J Chron Obstruct Pulmon Dis 2017, 12:1401-1411
Angrill J, Agustí C, De Celis R, Filella X, Rañó A, Elena M, et al. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis, Am J Respir Crit Care Med 2001, 164:1628-1632
Davies G, Wells AU, Doffman S, Watanabe S, Wilson R. The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis, Eur Respir J 2006, 28:974-979
Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis, Am J Respir Crit Care Med 2012, 186:657-665
Fuchs SI, Gappa M, Eder J, Unsinn KM, Steinkamp G, Ellemunter H. Tracking Lung Clearance Index and chest CT in mild cystic fibrosis lung disease over a period of three years, Respir Med 2014, 108:865-874
Wilson CB, Jones PW, O'Leary CJ, Hansell DM, Dowling RB, Cole PJ, et al. Systemic markers of inflammation in stable bronchiectasis, Eur Respir J 1998, 12:820-824
Bakakos P, Schleich F, Alchanatis M, Louis R. Induced sputum in asthma: from bench to bedside, Curr Med Chem 2011, 18:1415-1422
Bartoli ML, Costa F, Malagrinò L, Nieri D, Antonelli S, Decusatis G, et al. Sputum inflammatory cells in COPD patients classified according to GOLD 2011 guidelines, Eur Respir J 2016, 47:978-980
Oikonomou A, Tsanakas J, Hatziagorou E, Kirvassilis F, Efremidis S, Prassopoulos P. High resolution computed tomography of the chest in cystic fibrosis (CF): is simplification of scoring systems feasible? Eur Radiol 2008, 18:538-547
Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR: An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications, Am J Respir Crit Care Med 2011, 184:602-615
The Chinese national guidelines of pulmonary function test (2014). Chin J Tuberc Respir Dis. 2014;37:566–571. Available from: http://zhjhhhxzz.yiigle.com/CN112147201408/860037.htm.
Bhatt SP, Washko GR, Hoffman EA, Newell JJ, Bodduluri S, Diaz AA, et al. Imaging Advances in Chronic Obstructive Pulmonary Disease. Insights from the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study, Am J Respir Crit Care Med 2019, 199:286-301
Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA), 2019. Available from: http://www.ginasthma.org/
Blasi F, Chalmers JD, Aliberti S. COPD and bronchiectasis: phenotype, endotype or co-morbidity? COPD 2014, 11:603-604
Stockley JA, Stockley RA. Pulmonary Physiology of Chronic Obstructive Pulmonary Disease, Cystic Fibrosis, and Alpha-1 Antitrypsin Deficiency, Ann Am Thorac Soc 2016, 13 Suppl 2:S118-S122
Padilla-Galo A, Olveira C, Fernández DRL, Marco-Galve I, Plata AJ, Alvarez A, et al. Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients, Respir Res 2018, 19:43
Robroeks CM, Roozeboom MH, de Jong PA, Tiddens HA, Jöbsis Q, Hendriks HJ, et al. Structural lung changes, lung function, and non-invasive inflammatory markers in cystic fibrosis, Pediatr Allergy Immunol 2010, 21:493-500
Dente FL, Bilotta M, Bartoli ML, Bacci E, Cianchetti S, Latorre M, et al. Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis, Mediators Inflamm 2015, 2015:642503

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Role of noninvasive methods for assessing stable non-cystic fibrosis bronchiectasis

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Abstract

Figures

Background

Methods

Study subjects

Data Collection

Hrct Scoring

Feno Measurement

PFT

Bhr Test

Bdr Test

Statistical analysis

Results

Study population

Clinical Features And Pft Data Of Patients With Bronchiectasis

Clinical Features Of Patients In Different Subgroups Of Bronchiectasis

Comparison of HRCT scores among the three groups

Comparison of FeNO levels among the three groups

Correlation of FeNO with blood eosinophil, IgE, systemic inflammatory markers, PFT and HRCT score

Discussion

Conclusions

Abbreviations

Declarations

References

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