Acercamiento a la tos crónica en adultos / An approach to chronic cough

RESUMEN La tos crónica en los adultos puede ser causada por muchas causas, existen cuatro principales: el síndrome de tos de la vía aérea superior, enfermedad por reflujo gastroesofágico, reflujo laringofaríngeo, asma bronquial, y bronquitis eosinofílica no asmática. Todos los pacientes deben evaluarse clínicamente con espirometria, y comenzar con tratamiento empírico. Otras causas potenciales incluyen el uso de inhibidores de la enzima convertidora de la angiotensina, cambios medioambientales, uso del tabaco, enfermedad pulmonar obstructiva crónica, y la apnea obstructiva del sueño. La radiografía del tórax puede orientar hacia causas infecciosas, inflamatorias, y malignas. Los pacientes con tos crónica refractaria pueden remitirse a la consulta especializada de un neumólogo u otorrinolaringólogo, además de un ensayo terapéutico con gabapentin, pregabalin, y psicoterapia.

ABSTRACT Although chronic cough in adults can be caused by many etiologies, four conditions account for most cases: upper airway cough syndrome, gastro-esophageal reflux disease, also known as laryngo- pharyngeal reflux disease, bronchial asthma, and non-asthmatic eosinophilic bronchitis. All patients should be evaluated clinically with spirometry, and empiric treatment should be initiated. Other potential causes include angiotensin-converting enzyme inhibitor use, environmental triggers, tobacco use, chronic obstructive pulmonary disease, and obstructive sleep apnea. Chest radiography can rule out concerning infectious, inflammatory, and malignant thoracic conditions. Patients with refractory chronic cough should be referred to a pulmonologist or otolaryngologist in addition to a therapeutic trial of gabapentin, pregabalin, and psychotherapy.

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

PURPOSE: 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 (FEF(25–75)) in specifically identifying CVA and NAEB in these patients. METHODS: 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. RESULTS: 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. FEF(25–75) was significantly lower in patients with CVA than in those with other causes. A FEF(25–75) value of 74.6% showed good sensitivity and specificity for identifying patients with CVA. CONCLUSIONS: 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 FEF(25–75) (or combined with FeNO) can further discriminate patients with CVA from those with CVA/NAEB.

Advances in the treatment of respiratory allergic diseases by montelukast / 医学研究生学报

Airway allergic diseases are characterized by chronic inflammatory responses in airways. Leukotriene antagonists have been recently recommended as the first-line medication for respiratory allergic diseases, along with nasal glucocorticoids and antihistamines, due to their prominent efficacy and safety in allergic inflammation. This review summarized the clinical application of Montelukast, the representative drug of leukotriene antagonists, to treat allergic rhinitis, bronchial asthma, cough variant asthma, eosinophilia bronchitis and other diseases, in order to further explore the advantages and prospect of Montelukast in the application of airway allergic inflammation.

Difference in sputum concentrations of mucin in eosinophilic bronchitis and asthma / 实用医学杂志

Objective To investigated the difference in induced sputum concentrations of mucin between the patients with eosinophilic bronchitis (EB) and classic asthma, and found out the difference in mechanism. Methods 20 patients with eosinophilic bronchitis (EB), 20 patients with classic asthma and 10 healthy controls were enrolled. Induced sputum levels of MUC5AC, MUC5B, LTC4 and PGE2 were measured by enzyme immunoassay in patients and healthy control. Results In patients with asthma, sputum MUC5A (26.8 ± 8.5)μg/mL and LTC4 (700.8 ± 172.3)pg/mL were significantly elevated whereas MUC5B levels (1.1 ± 0.5)μg/mL were reduced compared with patients with EB MUC5AC:( 17 . 6 ± 7 . 0 )μg/mL , LTC4:( 320 . 9 ± 89 . 4 ) pg/mL , MUC5B:(2.6 ± 0.5)μg/mL and healthy controls MUC5AC:(12.5 ± 4.3)μg/mL, LTC4:(91.2 ± 16.1)pg/mL, MUC5B:(2.6 ± 0.4)μg/mL (P < 0.01). PGE2 levels were higher in patients with EB (433.8 ± 118.1)pg/mL than in asthma(172.7 ± 74.5)pg/mL and controls(113.3 ± 18.3)pg/mL(P < 0.01), but results did not differ between asthma and controls. The LTC4 showed a significant positive correlation with MUC5AC (r = 0.785,P < 0.01), and a significant negative correlation with MUC5B (r = -0.703,P < 0.01). Conclusion A significant difference in MUC5AC/MUC5B ratio was founded in proximal airway between EB and asthma. The unbalance level between LTC4 and PGE2 would be involved in the pathogenesis of airway mucus hypersecretion.

Valor del estudio celular del esputo en el seguimiento de las enfermedades inflamatorias de la vía aérea / Value of sputum analysis in the management of inflammatory airway diseases

El análisis celular del esputo, espontáneo u obtenido mediante la técnica de esputo inducido, se ha transformado en una herramienta ampliamente difundida para la evaluación y orientación del tratamiento de las enfermedades inflamatorias de la vía aérea, principalmente asma, enfermedad pulmonar obstructiva crónica y bronquitis eosinofílica. Se han aportado evidencias sobre la utilidad de la técnica del esputo inducido, validada y estandarizada, para ser empleada en pacientes con dificultades para expectorar. Numerosas investigaciones dieron cuenta de la efectividad de basar las decisiones terapéuticas en el componente inflamatorio de la vía aérea mediante el recuento de células en el esputo. Varios estudios mostraron que, en pacientes con asma el análisis celular de esputo guía en la determinación de estrategias para disminuir las exacerbaciones y para mejorar la función pulmonar, aun en pacientes con asma grave, para disminuir el remodelamiento; también se ha descrito su utilidad en pacientes con EPOC, para la disminución de las exacerbaciones.

Cellular analysis of sputum either spontaneous or by induced sputum technique, has become a widespread tool for the evaluation and guidance of treatment of inflammatory diseases of the airway, primarily asthma, COPD and eosinophilic bronchitis. Induced sputum method is a validated, standardized and non-invasive technique, useful in patients with difficulties to expectorate. Its implementation is simple and cost effective. Numerous investigations have shown the effectiveness of basing treatment decisions on the inflammatory component of the airway by counting cells in sputum. Several studies have demonstrated that in patients with asthma, results of this analysis can guide in defining strategies to reduce exacerbations and to improve lung function even in patients with severe asthma, as well as to decrease the remodeling; in addition, a reduction in exacerbations in COPD patients, monitored by this sputum examination, has also been described.

Clinical Course of Eosinophilic Bronchitis in Children / 소아알레르기및호흡기학회지

PURPOSE: It has been identified that eosinophilic bronchitis (EB) in adults can progress to asthma or fixed airway obstruction. In the present study, we evaluated the clinical course and prognosis of EB in children and their relationship with accompanying rhinosinusitis. METHODS: A total of 55 children with EB followed up for over than a year after the diagnosis were enrolled for the present study. We classified the subjects into two groups according to the prognosis and the presence of rhinosinusitis, respectively, and compared them with respect to clinical characteristics, eosinophil percentage in induced sputum, fractional exhaled nitric oxide (FeNO) and pulmonary function test. The poor prognostic group was defined as the children with asthma or asthma-like symptoms, or persistent or recurrent chronic cough in the long-term follow-up. RESULTS: The poor prognosis was achieved in 12 children (22%), and 3 children (5%) amongst them were diagnosed with asthma. There were no significant differences in clinical characteristics, eosinophil percentages in induced sputum, FeNO, spirometry and IOS according to the prognosis and the presence of rhinosinusitis. Additionally, the children with rhinosinusitis did not show any poorer outcome than those without rhinosinusitis. CONCLUSION: There were some limitations of this study for which the relationship between EB and rhinosinusitis in children was evaluated. However, in case of either poor short-term response to inhaled corticosteroids or elevated eosinophilic inflammation in airways or abnormal airway reversibility in impulse oscillometry, the long-term prognosis of EB in children needs to be considered, regardless of the presence of rhinosinusitis.

A Case of Eosinophilic Bronchitis Associated with Tracheal Diverticulum / 영남의대학술지

Tracheal diverticulum is relatively rare. It results from congenital or acquired weakness of the tracheal wall. Most cases are asymptomatic, but when symptoms are present, they are usually nonspecific. A 54-year-old man complained of sputum lasting for several months. Chest computed tomography showed an air-containing cystic structure in the trachea. Fiberoptic bronchoscopy demonstrated ostium arising from the right posterolateral wall at the trachea. Reported herein is a case of eosinophilic bronchitis associated with tracheal diverticulum.

VEGF and Activated Eosinophils in Children with Asthma and Eosinophilic Bronchitis / 소아알레르기및호흡기학회지

PURPOSE: Vascular endothelial growth factor (VEGF) is an important mediator of airway inflammation and remodeling in asthma. We aimed to explore whether VEGF is expressed at elevated levels in asthmatic airways or eosinophilic bronchitis (EB) and associated with eosinophilic inflammation, pulmonary function, and airway hyperresponsiveness (AHR) in children. METHODS: One hundred seventeen asthmatic children, 77 children with EB, and 84 healthy children were enrolled. Sputum supernatants were collected and VEGF and eosinophil cationic protein (ECP) levels were measured. RESULTS: Asthmatic children had significantly higher levels of VEGF in induced sputum [89.04 (29.95-178.09) pg/mL] compared to children with EB [25.30 (11.02-80.23) pg/mL] and healthy children [37.37 (16.56-71.30) pg/mL; P=0.0003]. VEGF in sputum positively correlated with sputum ECP (r=0.524; P<0.0001). Negative significant correlations were found between sputum VEGF and FEV1, (r=-0.252; P=0.001) or post-bronchodilator FEV1 (r=-0.181; P=0.038) whereas nonsignificant correlations were found between sputum VEGF and sputum eosinophils. CONCLUSION: Our findings suggest that VEGF is associated with activated eosinophils in the asthmatic airway, but not EB. Sputum VEGF could be a supportive marker that represents activation of airway eosinophils and persistent airflow limitation in asthmatic children.

Diagnosis and Treatment of Cough

Cough remains the most common reason for patients to seek medical attention. Although the exact prevalence is difficult to estimate, recurrent cough is reported in up to 40% of the population. For the investigation and treatment of chronic cough, it is important to understand its etiology, particularly when the underlying pathology exists outside the respiratory tract. Although there is no consensus as to the best diagnostic strategy for chronic cough, many protocols combine laboratory investigations with empirical trials of treatment. Specific treatment for the underlying disease of cough along with etiologic diagnosis should be emphasized rather than nonspecific antitussive therapy because nonspecific pharmacologic treatments have changed little during the last 50 years, without any significant advances from opiatebased compounds. Recently, molecular structures of cough receptors and mediators have been identified. Vanilloid receptor-1 is one of ion channel receptors expressed on the sensory neurons of cough reflex. Substances inhibiting ion channels and receptor antagonists of tachy-or bradykinins are being investigated. Thus safer and more effective agents to deal with this common problem are believed to be available in the near future.

Submucosal CD4+ and CD8+ T Lymphocyte Infiltrations in Asthma and Eosinophilic Bronchitis / 결핵

BACKGROUND: Asthma and eosinophilic bronchitis(EB) are eosinophilic inflammatory diseases of the airway. However, EB differs from asthma in that there is no variable airway obstruction or airway hyper-responsiveness. Pathologically, asthma is characterized by the accumulation of eosinophils and CD4+ T lymphocytes in the submucosa. A recent study showed that there was no significant difference between asthma and EB in terms of the submucosal eosinophil and T lymphocyte count. However, it is not known whether or not an infiltration of CD4+ and CD8+ T lymphocytes occurs in the airways of EB patients. The aim of this study was to identify the difference between the two conditions by measuring the submucosal CD4+ and CD8+ T lymphocyte count. METHODS: Immunohistochemical analysis of bronchial-biopsy specimens was performed in 17 subjects with asthma and 24 subjects with EB. RESULTS: The CD4+ T lymphocytes count in the asthma subjects and the EB subjects was similar (median, 58.6 vs 50.0 cells/mm2, respectively; P=0.341). In contrast, the number of CD8+ T lymphocytes in the EB subjects was higher than that in the asthma subjects (median, 46.7 vs 11.8 cells/mm2, respectively; P=0.003). CONCLUSION: The infiltration of submucosal CD8+ T lymphocytes may be associated with the pathophysiology of EB.

Evaluation of clinical course in patients with eosinophilic bronchitis: A prospective follow up study / 천식및알레르기

BACKGROUND: Eosinophilic bronchitis (EB) presents as a chronic cough and sputum eosinophilia without airflow limitation and bronchial hyperreactivity. The long-term clinical courses remain unknown. OBJECTIVE AND METHOD: The aim of this study was to evaluate how frequently EB recurs and whether it develops into chronic airway obstruction. Cough severity, FEV1, PC20 methacholine and sputum eosinophil percentages were serially measured in 36 subjects for up to 48 months. RESULT: Five subjects developed recurrent episodes of EB (RG) between 4 to 6 months after the first episode of EB. Asthma developed in the 9th month of the study in one of these subjects and a progressive FEV1 reduction exceeding 20% was observed in two. Nineteen subjects had no recurrence of EB (NRG). However, sputum eosinophilia recurred between 4 and 24 months in 10 subjects of the NRG, though this was without cough or FEV1 reduction. The follow-up eosinophil percentages were significantly higher in the RG than NRG group with recurrent sputum eosinophilia. CONCLUSION: About 14% of EB cases experience repeated episodes of EB and in about 30%, the EB recurs as asymptomatic sputum eosinophilia. Moreover, the extent of sputum eosinophilia was found to be associated with the recurrence of eosinophilic bronchitis, which leads to an airflow rate deterioration. These results suggest that repeated episode of EB is a risk factor for the development of asthma or chronic airway obstruction.

A case of hypereosinophilic syndrome with eosinophilic pneumonia, and bronchitis / 천식및알레르기

Idiopathic hypereosinophilic syndrome is characterized by multiorgan involvement without any cause, and peripheral eosinophilia(1,500/microliter) for more than 6 months. Clinically, many organs can be involved, but the heart is the most commonly involved organ. Although lung involvement is usual(20-30%)1) in hypereosinophilic syndrome, there are few reports of eosinophilic pneumonia proven by biopsy confirmation in Korea. We experienced a case of hypereosinophilic syndrome with eosinophilic pneumonia and bronchitis confirmed by biopsy, and we report it here with a review of the literature.

The Bronchial Biopsies and Steroid Response in Unexplained Chronic Non-Productive Cough / 결핵

BACKGROUND: The purpose of this study was to examine the causes and pathologic process of chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph by investigating clinicopathologic findings. METHOD: We studied 25 adults with chronic non-productive cough over a 3-week period with a normal chest radiograph and pulmonary function tests without any other symptoms. Clinical assessment, cough score, chest and sinus radiograph, pulmonary function tests, methacholine challenge, allergic skin prick test, and bronchoscopy for bronchial biopsies were performed. Subjects were then treated with prednesolone 20 to 30 mg/day for 1 to 2 weeks. RESULTS: The experimental group was divided into two subgroups - those infiltrated with eosinophils, and those infiltrated with lymphocytes depending on eosinophil and lymphocyte counts, both of which were respectively higher than those of the control group. Eosinophils infiltrated group had mean numbers of eosinophil of 89.8 cells/mm(2) while control group's mean was 0.4 cells/mm(2)(P=0.005). Lymphocyte infiltrated group was 4 patients whose mean was 84.3 cells/mm(2) with 28.4 cells/mm(2) of control group(P=0.026). In addition, the mean thickeness of the basement membrane of experimental group was 14.20+/-5.20microM in contrast of control group whose mean was 3.50+/-1.37microM(P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough asthma; the other 14 with eosinophilic bronchitis. Three subjects with eosinophilic bronchitis were atopic positive(21.4%) with the skin prick test. In the lymphocyte dominant group, all four subjects were diagnosed with lymphocytic bronchitis. Cough score was improved after steroid treatment in 22 of 25 subjects in the experimental group (88.0%). CONCLUSION: These results suggest chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph was associated with airway inflammation by eosinophil and lymphocyte infiltration. The causes for chronic non-productive cough were eosinophilic bronchitis, cough variant asthma, and lymphocytic bronchitis(written in frequency). They further suggest that therapeutic treatment with steroids can provide effective symptomatic relief.