Despite improvements in childhood immunization and tuberculosis control, bronchiectasis remains a significant clinical issue worldwide [
High-resolution computed tomography (HRCT) is a proven, reliable, and noninvasive method for assessing bronchiectasis [
Inflammation in bronchiectasis is characterized by persistence and intensity. Airway inflammation is neutrophil-predominant, and inflammatory profiles show increased levels of proinflammatory cytokines such as IL-1, IL-6, and TNF-
One hundred and twenty-five (125) patients with bronchiectasis were recruited from the Thoracic Outpatient Clinic of Chang Gung Memorial Hospital in Taiwan from January 2006 to December 2007. The inclusion criteria were as follows: bronchiectasis documented on chest HRCT, idiopathic etiology of bronchiectasis (none of the patients with background suggests cystic fibrosis such as chronic dysfunction of the pancreas or liver or intestine or an electrolyte imbalance, disease onset before adolescence, and family history), chronic sputum production (daily sputum ≥ 10 mL), absence of other major pulmonary diagnoses, and a steady state defined by the absence of changes in symptoms noted by the patient over the past 3 weeks. The exclusion criteria were as follows: bronchiectasis with defined etiology (i.e., primary ciliary dyskinesia and allergic bronchopulmonary aspergillosis), common variable immunodeficiency, and use of antibiotics within the last three weeks. Patients with hepatic failure, malignancy, or pregnancy were also excluded.
The study design was conducted with approval of the Institutional Review Board (IRB) of Chang Gung Medical Foundation (IRB no. 97-1105A3). All patients provided written informed consent to participate in this study. The methodology and patient confidentiality were also approved by our IRB.
Blood was drawn for measurement of serum inflammatory markers. The blood samples were then centrifuged at 3000 rpm at 4°C for 15 minutes, and aliquots were stored at −70°C. A latex turbidimetric immunoassay with a sensitivity of 0.01 mg/L was used to measure circulating levels of hs-CRP (Biomedical Laboratory Inc.).
The scoring system for HRCT described by Brody was used, and a score sheet was completed for each lobe of the lung [
Two experienced radiologists, both pulmonary division consultants with more than 5 years of experience, scored the HRCT of these patients without any clinical data information. The interobserver agreement was 0.946 (data not shown).
The 6-minute walk tests using the standard protocol described in the 2002 American Thoracic Society (ATS) statement [
Height was measured with a rigid stadiometer, and weight was measured by a calibrated digital scale. Body mass index (BMI) was calculated by dividing the weight (kilograms) by the height (meters squared), and then the quotient was converted into age- and sex-adjusted percentiles based on population data from NHANES 2000.
Data were presented as mean ± SD, and all statistical analyses were performed using SPSS version 13.0 (SPSS Inc., Chicago, IL, USA). Independent Student
During the study period, 125 patients with bronchiectasis were recruited in the chest outpatient department, and 78 patients were evaluated for this study. Sixty-nine patients who met the inclusion criteria were enrolled in the study (Figure
Demographic data of the 69 stable bronchiectasis patients.
Demographic factor | Mean (SD) | 95% CI |
---|---|---|
Age (years) | 57.5 | 54.2–60.8 |
BMI (kg/m2) | 22.0 | 21.2–22.8 |
FVC (L) | 2.1 | 1.9–2.3 |
FVC% predicted | 67.4 | 62.7–72.0 |
FEV1 (L) | 1.5 | 1.4–1.7 |
FEV1% predicted | 62.6 | 57.1–68.1 |
6 MWD (m) | 454.4 | 432.4–476.4 |
Rest O2S% | 95.1 | 94.3–95.9 |
HRCT score | 26.2 | 23.1–29.3 |
hs-CRP (mg/L) | 4.5 | 3.6–5.5 |
Abbreviations: BMI: body mass index, FVC: forced vital capacity, FEV1: volume that has been exhaled at the end of the first second of forced expiration, 6 MWD: 6-minute walk test distance, HRCT: high-resolution computed tomography, and hs-CRP: high-sensitivity C-reactive protein.
Flowchart of patients in the study cohort.
Following the initial evaluation of hs-CRP, the patients were divided into two groups according to their previous exacerbation-related hospitalizations: those with an hs-CRP level less than 4.26 mg/L (
Characteristics and outcomes of the 69 stable bronchiectasis patients.
hs-CPR < 4.26 | hs-CRP ≥ 4.26 |
|
|
---|---|---|---|
|
|
||
Age (years) |
|
|
0.406 |
Gender (M/F) | 21/17 | 18/13 | 0.815 |
BMI (kg/m2) |
|
|
0.990 |
Smoking | |||
Never | 30 | 25 | 0.862 |
Ex/current | 8 | 6 | |
PFT | |||
FVC (L) |
|
|
0.034 |
FVC (%) |
|
|
0.014 |
FEV1 (L) |
|
|
0.038 |
FEV1 (%) |
|
|
0.046 |
FEV1/FVC (%) |
|
|
0.401 |
Total IgE (KU/L) |
|
|
0.737 |
ECP (mcg/L) |
|
|
0.304 |
6 MWT | |||
Rest O2 sat (%) |
|
|
0.001 |
Lowest O2 sat (%) |
|
|
0.237 |
ΔO2 sat (%) |
|
|
0.816 |
Walk distance (meters) |
|
|
0.136 |
HRCT scores |
|
|
0.004 |
Bacterial colony | |||
|
6 | 11 | 0.115 |
Others | 8 | 4 | |
Normal flora/no growth | 24 | 16 | |
Hospitalizations before recruitment (times/year) | |||
<2 | 35 | 21 | 0.01 |
≥2 | 3 | 10 |
Abbreviations: hs-CRP: high-sensitivity C-reactive protein, PFT: pulmonary function test, IgE: immunoglobulin E, ECP: eosinophilic cationic protein, 6 MWT: 6-minute walk test, ΔO2 sat (%): oxygenation difference between rest and lowest during 6-minute walk test, and HRCT: high-resolution computed tomography.
ROC curve of hs-CRP for prediction patients with repeated hospitalization (≥2 exacerbation-related hospitalization events).
There were no statistical differences in age, sex distribution, smoking status, BMI, pulmonary function test, and 6 MWT between the two groups. Bacteriology and regular treatment regimens (data not shown) were also similar. The HRCT scores were significantly increased in the higher hs-CRP group compared with the lower group (Table
Correlations between hs-CRP, clinical variables, and HRCT score.
hs-CRP(mg/L) |
|
|
---|---|---|
Age (years) | 0.124 | 0.312 |
BMI (kg/m2) | −0.094 | 0.441 |
FVC (L) | −0.161 | 0.187 |
FEV1 (L) | −0.153 | 0.211 |
FEV1/FVC | −0.058 | 0.637 |
IgE (KU/L) | 0.180 | 0.140 |
ECP (mcg/L) | 0.087 | 0.479 |
Rest O2% | −0.269 |
|
Lowest O2% | −0.108 | 0.376 |
ΔO2% | −0.003 | 0.982 |
6 MWD (m) | −0.190 | 0.118 |
HRCT score | 0.473 | < |
Abbreviations: BMI: body mass index, FVC: forced vital capacity, FEV1: first second, 6 MWD: 6-minute walk test distance, HRCT: high-resolution computed tomography, and hs-CRP: high-sensitivity C-reactive protein.
HRCT scores in higher and lower serum hs-CRP groups. HRCT scores were significantly higher in bronchiectasis patients with higher hs-CRP (mg/L). Boxes, median and interquartile range; whiskers, full range of values obtained;
Relationship between serum high-sensitivity C-reactive protein (hs-CRP, mg/L) levels and HRCT scores in patients with stable bronchiectasis (
Relationship between serum high-sensitivity C-reactive protein (hs-CRP, mg/L) levels and RO2S% (rest oxygenation saturation under room air) in patients with stable bronchiectasis (
The pathogenetic mechanism leading to bronchiectasis is complex and still not well understood [
Progressive idiopathic bronchiectasis includes at least two subsets of patients [
C-reactive protein is predominantly produced in the liver, and IL-1, IL-6, and TNF-
Bronchiectasis patients in a stable phase with elevated levels of systemic markers of inflammation have been studied [
Levels of CRP (not hs-CRP) have been shown to significantly correlate with HRCT bronchiectasis scores; however, a very poor correlation with lung function measures has also been reported [
The 6-minute walk test, a functional assessment of patients with cardiopulmonary disease, is a good outcome predictor of obstructive airway diseases such as COPD and idiopathic pulmonary fibrosis. However, it has been reported that exercise tolerance demonstrates a stronger correlation to health-related quality of life than physiological measures of lung function or disease severity in bronchiectasis [
Resting oxygen saturation was significantly lower in the higher hs-CRP group. Furthermore, the association between the need for long-term oxygen therapy and mortality has been reported [
A high prevalence of atopy and increased serum ECP in adult patients with bronchiectasis has been reported [
Bacterial infections are a major cause of morbidity and mortality in bronchiectasis patients. Acute inflammation is an important host defense against bronchial infection; however, if the infection becomes chronic, it can cause lung damage and lead to disease progression [
Because there are so few randomized controlled trials of therapies for non-CF bronchiectasis and no US Food and Drug Administration approved therapies for non-CF bronchiectasis, patients must be evaluated and treated on an individual basis. Patients with mild-to-moderate bronchiectasis and infrequent exacerbations may not need maintenance therapy. According to the study of K.W. Tsang, inhaled corticosteroid (ICS) treatment is beneficial to patients with bronchiectasis, particularly those with
Two patients died of pneumonia and respiratory failure later within the study period, and their initial hs-CRP levels were 18.78 and 18.81 mg/L, respectively. Hence, the significance of higher hs-CRP in stable bronchiectasis needs further investigation.
There are several limitations to the current study. First, the number of patients is limited, and they were recruited from a single hospital, which may limit the generalizability of the study results. Second, evolutionary variables such as clinical evolution and the numbers of following exacerbation or hospitalization were not included in the analysis due to the short study period. Third, important transversal variables related to bronchiectasis such as systemic inflammatory diseases other than cardiovascular disorders and quality of life were not included in the analysis because the limited number of patients did not allow for the inclusion of more variables in the factorial analysis. Only four patients had type 2 diabetes mellitus and the study of osteoporosis was incomplete. Finally, the impact of nontuberculosis mycobacterial colonization or infection in these patients was not studied. Therefore, larger, multicentric studies are needed, with long-term follow-up and a larger number of patients in order to corroborate our results.
In conclusion, in patients with stable non-CF bronchiectasis, there was a good correlation between serum hs-CRP and HRCT scores. Increased HRCT scores and decreased rest oxygenation saturation were associated with higher levels of serum hs-CRP, which suggests that serum hs-CRP may be a useful biomarker that directly reflects the degree of systemic inflammation in stable non-CF bronchiectasis. However, further studies are required in order to better elucidate the clinical significance of the role of hs-CRP in bronchiectasis progression and treatment response, either in anti-inflammatory pharmacological therapy or in regular pulmonary rehabilitation programs.
High-sensitivity C-reactive protein
Cystic fibrosis
Pulmonary function test
Immunoglobulin E
Eosinophilic cationic protein
6-minute walk test
High-resolution computed tomography
Inhaled steroids
Long-acting beta-agonists.
The authors declare no conflict of interests in the study itself or in the publication of the paper.
This work was supported by research Grant no. 370791 from Chang Gung Medical Foundation, Chang Gung University, Taiwan, and National Science Council, Taipei, Taiwan, NSC 100-2314-B-182-046.