Narrative Review: how long should patients with cough variant asthma or non-asthmatic eosinophilic bronchitis be treated?

The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, and approximately 30% to 50% of people with chronic cough have eosinophilic airway inflammation, the presence of which can be confirmed by sputum eosinophilia or elevated exhaled nitric-oxide levels. Cough variant asthma (CVA) is a phenotype of asthma which lacks wheezing or dyspnea, and consistently one of the most common causes of chronic cough worldwide. CVA and non-asthmatic eosinophilic bronchitis (NAEB) shares common feature such as chronic dry cough, eosinophilic inflammation, and development of chronic airflow obstruction (CAO) and asthma in a subset of patients. The distinctive characteristic of these conditions is the presence of airway hyperresponsiveness in CVA but not in NAEB. Coughing is responsive to bronchodilators such as beta-agonists in CVA, but such feature has not been clarified in NAEB. Inhaled corticosteroids (ICSs) are the first-line treatment, and leukotriene receptor antagonists are also effective, in patients with both CVA and NAEB. This review will give an outline of clinical and physiological features, and prognosis and its determinants of CVA and EBNA. Further, the rationale and evidence, despite limited, for the need of long-term treatment will be discussed. The development of airway remodeling due to mechanical stress to the airways exerted by long-standing coughing will also be discussed.

Niimi A 《-》

Eosinophilic airway disorders associated with chronic cough.

Niimi A ，Matsumoto H ，Mishima M 《PULMONARY PHARMACOLOGY & THERAPEUTICS》

Increased S-nitrosothiol levels in nonasthmatic eosinophilic bronchitis compared with cough variant asthma.

Nonasthmatic eosinophilic bronchitis (NAEB) and cough variant asthma (CVA) are common causes of chronic cough. Both are characterized by eosinophilic inflammation in the airways. However, airway hyperresponsiveness, which is a characteristic feature of CVA, is not observed in NAEB. We hypothesized that endogenous bronchodilator S-nitrosothiol (SNO) levels are different between patients with NAEB and CVA. SNO concentrations in sputum supernatant were measured using a commercially available kit in 20 NAEB and 21 CVA patients. The mean sputum eosinophil counts and exhaled nitric oxide values were similar in patients with NAEB (12.4 ± 2.3%, 80.6 ± 8.1 ppb) and CVA (15.3 ± 3.7%, 97.7 ± 9.2 ppb). By contrast, SNO levels in the airway lining fluid of NAEB patients were substantially higher than those of CVA patients (87.1 ± 9.8 vs. 46.8 ± 4.8 μM; p < 0.05). SNOs may be an important factor in determining the development of airway hyperresponsiveness in the presence of eosinophilic inflammation.

Lee BJ ，Jeung YJ ，Lee JY ，Choi DC ... -  《-》

Non-asthmatic eosinophilic bronchitis and its relationship with asthma.

Non-asthmatic eosinophilic bronchitis (NAEB) is an important cause of chronic cough. NAEB shares similar eosinophilic inflammation of airway and response to corticosteroids with asthma. However, in contrast to asthma, NAEB subjects have no airflow obstruction and airway hyperresponsiveness. The pathogenesis of NAEB are involved with many inflammatory cells such as eosinophils, lymphocytes, mast cells, cytokines and inflammatory mediators, includingTh2 cytokines, histamine, leukotrines, prograndins and oxidative stress. The different locations of inflammatory cells and the inflammatory mediators level may explain this difference between EB and asthma. There is no study on dose and duration of treatment. On the prognosis of NAEB, long term follow-up study suggested that NAEB should be a distinct entity rather than an early stage of asthma or COPD. The relapse rate is high after treatment. Assessing sputum eosinophils after treatment is useful to identify those at risk of relapse.

Lai K ，Chen R ，Peng W ，Zhan W ... -  《-》

Value of Exhaled Nitric Oxide and FEF(25-75) in Identifying Factors Associated With Chronic Cough in Allergic Rhinitis.

Chronic cough in allergic rhinitis (AR) patients is common with multiple etiologies including cough variant asthma (CVA), non-asthmatic eosinophilic bronchitis (NAEB), gastroesophageal reflux-related cough (GERC), and upper airway cough syndrome (UACS). Practical indicators that distinguish these categories are lacking. We aimed to explore the diagnostic value of the fraction of exhaled nitric oxide (FeNO) and forced expiratory flow at 25% and 75% of pulmonary volume (FEF25-75) in specifically identifying CVA and NAEB in these patients. Consecutive AR patients with chronic cough were screened and underwent induced sputum, FeNO, nasal nitric oxide, spirometry, and methacholine bronchial provocation testing. All patients also completed gastroesophageal reflux disease questionnaires. Among 1,680 AR patients, 324 (19.3%) were identified with chronic cough, of whom 316 (97.5%) underwent etiology analyses. Overall, 87 (27.5%) patients had chronic cough caused by NAEB, 78 (24.7%) by CVA, 16 (5.1%) by GERC, and 81 (25.6%) by UACS. Patients with either NAEB or CVA (n = 165, in total) were further assigned to a common group designated as CVA/NAEB, because they both responded to corticosteroid therapy. Receiver operating characteristic curves of FeNO revealed obvious differences among CVA, NAEB, and CVA/NAEB (area under the curve = 0.855, 0.699, and 0.923, respectively). The cutoff values of FeNO at 43.5 and 32.5 ppb were shown to best differentiate CVA and CVA/NAEB, respectively. FEF25-75 was significantly lower in patients with CVA than in those with other causes. A FEF25-75 value of 74.6% showed good sensitivity and specificity for identifying patients with CVA. NAEB, CVA, and UACS are common causes of chronic cough in patients with AR. FeNO can first be used to discriminate patients with CVA/NAEB, then FEF25-75 (or combined with FeNO) can further discriminate patients with CVA from those with CVA/NAEB.

Liu X ，Wang X ，Yao X ，Wang Y ，Sun Y ，Zhang L ... -  《-》