Allergy Asthma Proc. 2015 Mar-Apr;36(2):e23-8.
Serum high-sensitivity C-reactive protein can be an airway inflammation predictor in bronchial asthma.
Shimoda T, Obase Y, Kishikawa R, Iwanaga T.
Clinical Research Center, Fukuoka National Hospital, Fukuoka, Japan.
It is controversial that the serum high-sensitivity C-reactive protein (hs-CRP) can be a useful marker of airway inflammation in bronchial asthma, because various factors have been reported to affect hs-CRP levels. We conducted a study in patients with mild bronchial asthma without complications to determine whether hs-CRP is a useful indicator of airway inflammation. The induced sputum cell differentiation, respiratory function tests, bronchial hyperresponsiveness tests, and hs-CRP measurement were performed in the subject population consisted of 40 healthy volunteers and 45 patients with bronchial asthma. The log-transformed (log) serum hs-CRP level was higher in asthmatic patients compared with healthy controls (2.49 ± 0.41 versus 2.21 ± 0.39; p = 0.002). A receiver-operating characteristic (ROC) analysis showed a sensitivity of 0.69 and specificity of 0.70 for a log serum hs-CPR of 2.3 to distinguish asthmatic patents from healthy controls. The log serum hs-CRP level negatively correlated with forced volume in 1 second (FEV1.0)%pred (r = -0.31, p = 0.04), positively correlated with sputum eosinophils (r = 0.34, p = 0.02), negatively correlated with sputum macrophages (r = -0.56, p < 0.001), and did not correlate with log 20% fall in FEV1.0 (PC20) (r = -0.09, p = 0.56). A multiple regression analysis revealed that the log serum hs-CRP concentration significantly correlated with eosinophils (p = 0.019) and neutrophils (p = 0.042) in the sputum, respectively. Serum hs-CRP may be a useful marker of airway inflammation in nonsmoking asthmatic patients without complications, such as heart disease, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, or infection.
Bronchial asthma is a chronic inflammatory disease characterized by airway infiltration of inflammatory cells, including eosinophils, mast cells, macrophages, neutrophils, and lymphocytes. Examination of airway inflammation is important for diagnosis and treatment of bronchial asthma.
Airway inflammation is assessed by various measures, including bronchofiberscopy (BF), bronchoalveolar lavage (BAL), induced sputum, exhaled breath condensate (EBC), and fractional exhaled nitric oxide (FeNO). Serum hs-CRP was recently reported as a useful marker of inflammation in bronchial asthma (1).
Airway inflammation of bronchial asthma is devided to three phenotypes of eosinophilic , neutrophilic and mixed type with eosinophilic and neutrophic inflammation. Eosinophilic and mixed type inflammation are usually more dominant than neutrophilic type.
FeNO is more useful than serum hs-CRP as a marker of eosinophilic inflammation (2). However, serum hs-CRP can be used as a marker of not only eosinophilic but also neutrophilic and mixed type inflammation in bronchial asthma.
Fig.1 Comparison of log hs-CRP between eosinophilic and mixed type inflammation
The comparison of log hs-CRP between eosinophilic and mixed type inflammation in mild persistent bronchial asthma is showen in Figure 1 (unpublished). Eosinophilic or mixed type inflammation was defined by the report of Moore WC, et al (3). The median (25-75%) of hs-CRP is 2.13(1.95-2.44) in healthy volunteers. Log hs-CRP is higher in both eosinophilic and mixed type group in asthmatic patients than that of healthy volunteers. Furthermore, log hs-CRP is higher in mixed type group than eosinophilic group (p=0.0490). The change of log hs-CRP before and after budesonide 800 mcg/day treatment in mild persistent bronchial asthma is showen in Figure 2 (unpublished). Log hs-CRP decreased 6 months after inhaled corticosteroid (ICS) treatment (p= 0.0065).
I enphasize the notes of hs-CRP as a marker of inflammation in bronchial asthma. Hs-CRP levels are influenced by various factors including systemic inflammation, age, body mass index, smoking status, serum lipid levels, blood pressure, diabetic status, and exercise, as well as airway inflammation (4), causing difficulties in obtaining stable values.
In conclusion, serum hs-CRP levels are elevated in asthma patients with eosinophil-mediated or neutrophil-associated inflammation. However, serum hs-CRP cannot be used as a inflammation marker in all asthma patients. Therefore, serum hs-CRP is useful in assessing airway inflammation in non-smoking, non-obese, younger asthmatic patients without complications, such as heart disease, hypertension, diabetes mellitus, hyperlipidemia, autoimmune disease, COPD and infection.
Fig.2 Change of log hs-CRP before and after ICS treatment
- Jousilahti P, Salomaa V, Hakala K, et al. The association of sensitive systemic inflammation markers with bronchial asthma. Ann Allergy Asthma Immunol 2002; 89:381–5.
- Shimoda T, Obase Y, Kishikawa R, Iwanaga T, Miyatake A, Kasayama S. The fractional exhaled nitric oxide and serum high sensitivity C-reactive protein levels in cough variant asthma and typical bronchial asthma. Allergology International 2013;62:251-257.
- Moore WC, Hastie AT, Li X, Li H, Busse WW, Jarjour NN, Wenzel SE, Peters SP, Meyers DA, Bleecker ER. National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol 2014 Jun;133:1557-63.
- Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease; Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511.