Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 controls, underwent methacholine bronchial provocation test and capsaicin cough provocation test. Elicited cough number and flow-volume curve was examined after inhalation of capsaicin to evaluate cough sensitivity and EAHR. Thirty-three patients, with postnasal drip, showed normal extrathoracic airway responsiveness, and 27 of them showed normal cough sensitivity to capsaicin. Cough sensitivity was enhanced in 14 patients with cough variant asthma (CVA) who showed bronchial hyperresponsiveness; EAHR to inhaled capsaicin was present in 12 of them. The remaining 30 patients were tentatively diagnosed as idiopathic chronic cough (ICC). Eleven ICC patients showed enhanced cough sensitivity and EAHR to inhaled capsaicin while 19 patients showed normal values. These results indicate that cough sensitivity is closely related with extrathoracic airway responsiveness during capsaicin provocation in some chronic cough patients. EAHR and enhanced cough sensitivity to inhaled capsaicin may be a part of mechanism developing chronic cough.
Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. They are also found among non-asthmatic subjects, including allergic rhinitis patients and the general population. Atopy and BHR in asthma are closely related. Atopy induces airway inflammation as an IgE response to a specific allergen, which causes or amplifies BHR. Moreover, significant evidence of the close relationship between atopy and BHR has been found in non-asthmatic subjects. In this article, we discuss the relationship between atopy and BHR in the general population, asthmatic subjects, and those with allergic rhinitis. This should widen our understanding of the pathophysiology of atopy and BHR.
Allergic rhinitis; asthma; atopy; bronchial hyperresponsiveness; patients; population
About half of a series of 100 consecutive patients with disturbances of the eyes, ears, nose or throat complained of postnasal drip. When smears of the mucous discharge were examined it was found that in about a third of the cases in which there was complaint of drip, neither eosinophils nor neutrophils could be demonstrated. This indicates that causes of the drip other than allergic disease and infection must be considered.
Cytologic examination of the postnasal drip showed that about one-third of the patients with nasal disease or histories positive for allergic reaction had nasal eosinophilia. Nasal eosinophilia was noted occasionally in patients with normal-appearing nasal structures and in patients with no history of allergic disease.
BACKGROUND: H1 antihistamines have been shown to have an antitussive effect in patients with asthma, postnasal drip, and allergic rhinitis. No study has been performed to determine whether orally administered H1 antihistamines can reduce the number of coughs induced by stimulation of cough receptors in non-asthmatic patients with chronic dry cough. METHODS: The effect of loratadine (10 mg) on the number of coughs induced by ultrasonically nebulised distilled water (UNDW) was examined in 10 patients with nasal disease and in seven patients with unexplained chronic cough using a randomised, double blind crossover method. Eleven normal volunteers were also studied. Each subject inhaled UNDW for one minute, and the numbers of coughs during the one minute inhalation and the 30 seconds following it were counted. RESULTS: There was no difference in the results of pulmonary function tests performed before and one minute after UNDW inhalation for either patients or normal subjects. There was also no significant difference between the results of pulmonary function tests before or after oral administration of loratadine. Loratadine significantly reduced the number of coughs in patients with nasal disease and in those with unexplained chronic cough, but not in normal subjects. CONCLUSIONS: The H1 antihistamine loratadine reduces cough induced by UNDW. The release of histamine may contribute to the chronic cough in patients with unexplained chronic cough or nasal disease.
Bronchial hyperresponsiveness (BHR) is an important pathophysiological feature of asthma. In addition to the diagnostic significance, BHR is associated with the severity of airway inflammation and BHR- based treatment approaches has been shown to be effective. Nevertheless, challenge tests are time consuming, inconvenient to patients, and are not accessible in every primary care physicians. We aimed to develop a questionnaire for the assessment of BHR in Korean subjects.
From the 24 University-affiliated hospitals, we recruited 149 adults between age 20 and 40 years with more than one asthmatic symptom (cough, sputum or dyspnea) and who had bronchial provocation test. A list of 33 symptoms, past history of allergy or smoking and 10 provoking stimuli were selected for the BHR questionnaire. After a methacholine challenge test patients were asked to complete each questionnaire. For each item of questionnaire, diagnostic odds ratios for the presence of BHR were calculated and multiple logistic regression analysis was performed to select final questionnaire items. Receiver operating characteristic (ROC) curve analysis was used to evaluate the sensitivity and specificity of the selected questionnaire items.
Methacholine challenge test was positive in 36 patients (24.2%). Eleven symptoms and 2 provoking stimuli items were statistically significant by the results of diagnostic odds ratio. According to the result of multiple logistic regression analysis, 4 items were finally selected for the significant BHR questionnaire: the presence of wheezing episode, past history of physician-diagnosed asthma, family history of asthma. The psychiatric stress was negatively associated provoking stimuli item for the presence of BHR. The area under the ROC curve was 0.80 (95% CI, 0.72-0.86). Sensitivity was 84.9% (95% CI, 68.1-94.9) and specificity was 65.5% (95% CI, 55.8-74.3).
Four BHR questionnaire items including wheezing episode, past history of physician-diagnosed asthma, family history of asthma and psyachiatric stress stimuli were able to assess the presence of BHR in Korean adults.
Background: Increased hydrogen and reduced chloride ionic environments of the airways are conducive to the stimulation of cough. However, the constituents of the local milieu of the airways of patients with chronic cough are unknown.
Methods: The pH and chloride levels in exhaled breath condensate and capsaicin cough threshold (C5) were measured in 50 patients with chronic cough and in 16 healthy controls. pH and chloride measurements were repeated after capsaicin challenge in those with cough. The cause of cough was asthma (n = 13), postnasal drip/rhinitis (n = 7), gastro-oesophageal reflux (n = 5), bronchiectasis (n = 5), but remained unidentified in 20.
Results: Compared with controls, patients with chronic cough had lower pH (mean 7.9 v 8.3, 95% CI of difference –0.5 to –0.2, p<0.0001), chloride levels (median 4 v 6 mmol/l, 95% CI –3.1 to –0.2, p = 0.007), and C5 (median 3.9 v 125 µM, 95% CI –270.0 to –17.6, p = 0.002). The pH levels were different in the six subgroups including controls, and were reduced in all diagnostic subgroups of patients with cough compared with controls but did not differ between them. Chloride levels were significantly different in the six subgroups but were lower than controls in only the gastro-oesophageal reflux subgroup. There was a weak but significant correlation between chloride levels and C5 when all participants were analysed together, but not between pH and C5 or chloride levels. pH and chloride levels did not change after capsaicin challenge.
Conclusions: The epithelial lining fluid of patients with chronic cough has a reduced pH and reduced chloride levels which could contribute to the enhanced cough reflex.
Chronic obstructive pulmonary disease (COPD) related to wood smoke exposure is characterized by important inflammation of the central and peripheral airways without significant emphysema. The objective of this study is to describe the bronchial hyperresponsiveness (BHR) level in women with COPD related to wood smoke exposure and to compare it with the BHR in women with COPD related to tobacco smoking.
Materials and methods
Two groups of women with stable COPD were studied: (1) wood smoke exposed (WS-COPD); and (2) tobacco smoke exposed (TS-COPD). A methacholine challenge test (MCT) was performed in all patients according to American Thoracic Society criteria. BHR levels were compared using the methacholine concentration, which caused a 20% fall in the FEV1 (PC20).
Thirty-one patients, 19 with WS-COPD and 12 with TS-COPD, were included. There were no significant differences between the groups in baseline FVC, FEV1, IC, FEF25–75, and FEF25–75/FVC. All 31 patients had a positive MCT (PC20 < 16 mg/mL) and the fall in the FEV1 and IC was similar in both groups. The severity of BHR was significantly higher in the WS-COPD patients (PC20: 0.39 mg/mL) than in the TS-COPD patients (PC20: 1.24 mg/mL) (P = 0.028). The presence of cough, phlegm, and dyspnea during the test were similar in both groups.
We found moderate to severe BHR in women with WS-COPD, which was more severe than in the TS-COPD women with similar age and airflow obstruction. This paper suggests that the structural and inflammatory changes induced by the chronic exposure to wood smoke, described in other studies, can explain the differences with TS-COPD patients. Future studies may clarify our understanding of the impact of BHR on COPD physiopathology, phenotypes, and treatment strategies.
biomass fuels; indoor air pollution; wood smoke; COPD; methacholine challenge test
We previously demonstrated in a group of patients with perennial allergic rhinitis alone impairment of spirometric parameters and high percentage of subjects with bronchial hyperreactivity (BHR). The present study aimed at evaluating a group of polysensitized subjects suffering from allergic rhinitis alone to investigate the presence of spirometric impairment and BHR during the pollen season.
One hundred rhinitics sensitized both to pollen and perennial allergens were evaluated during the pollen season. Spirometry and methacholine bronchial challenge were performed.
Six rhinitics showed impaired values of FEV1 without referred symptoms of asthma. FEF 25–75 values were impaired in 28 rhinitics. Sixty-six patients showed positive methacholine bronchial challenge. FEF 25–75 values were impaired only in BHR positive patients (p < 0.001). A significant difference was observed both for FEV1 (p < 0.05) and FEF 25–75 (p < 0.001) considering BHR severity.
This study evidences that an impairment of spirometric parameters may be observed in polysensitized patients with allergic rhinitis alone during the pollen season. A high percentage of these patients had BHR. A close relationship between upper and lower airways is confirmed.
allergic rhinitis; polysensitization; bronchial hyperreactivity; methacholine challenge; FEF 25–75
Chronic cough is one of the most challenging symptoms to diagnose and treat, not only because of the variety of underlying disorders but also its varying susceptibility to treatments. Etiological studies of chronic cough vary depending on the clinical settings and the particular interests of investigators.
The purposes of this study were first to categorize the etiology of chronic cough by its response to systematic diagnostic treatments starting from the β2 agonist and second to sub-categorize β2 agonist responsive cough (BRC) by the airway hyperresponsiveness.
One hundred and eighty-four never-smokers received the maximal dose of procaterol to diagnose BRC. BRC was sub-categorized into two groups with or without airway hyperresponsiveness measured by the methacholine challenge test. Sinobronchial syndrome (SBS) was diagnosed by postnasal drip symptoms and by the response to clarythromycin and carbocysteine. Atopic cough (AC) was diagnosed by the evidence of atopy and the response to cetirizine hydrochloride. Gastroesophageal reflux disease (GERD) was diagnosed by the response to rabeprazole sodium. Since we did not investigate eosinophil counts in the tissue or in the induced sputum, no diagnosis of eosinophilic bronchitis was made.
One hundred and nine patients had BRC. Twenty-three of them had bronchial asthma (BA), 53 had cough variant asthma (CVA) and 33 had non-hyperresponsive BRC (NHBRC). Thirty-one patients had GERD, 27 had AC and 14 had SBS. Twenty-five patients had more than one diagnosis in combination, while 6 had other miscellaneous diseases. Twelve patients were undiagnosed and 11 dropped out of the study.
The majority of chronic cough was BRC. NHBRC was a new chronic cough entity. GERD is a common cause of chronic cough in Japan, as in Western countries. AC and SBS are also causes of chronic cough in Japan.
University hospital medical information network
Airway hyperresponsiveness; β2 agonist; Bronchial asthma; Cough variant asthma; Non-hyperresponsive and β2 agonist responsive cough; Gastroesophageal reflex disease; Sinobronchial syndrome; Atopic cough; Postnasal drip; Chronic cough
Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma?
Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed.
Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy.
Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question.
Sputum eosinophilia is observed frequently in patients with rhinitis. Sputum eosinophilia in patients with non-asthmatic allergic rhinitis has been suggested to be related to nonspecific airway hyperresponsiveness (AHR). However, the clinical significance of sputum eosinophilia in patients with non-asthmatic rhinitis without AHR has not been determined. We conducted a retrospective study examining the influence of sputum eosinophilia in patients with non-asthmatic rhinitis without AHR on pulmonary function and expression of fibrosis-related mediators.
Eighty-nine patients with moderate-to-severe perennial rhinitis without AHR were included. All underwent lung function tests (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), skin tests to inhalant allergens, methacholine bronchial challenge tests, and hypertonic saline-induced sputum to determine eosinophil counts. Sputum mRNA levels for transforming growth factor-β (TGF-β), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also examined. Patients were divided into two groups according to the presence of sputum eosinophilia (≥3%, eosinophilia-positive [EP] and <3%, eosinophilia-negative [EN] groups).
FEV1 was significantly lower (P=0.04) and FEV1/FVC tended to be lower (P=0.1) in the EP group than in the EN group. In sputum analyses, the MMP-9 mRNA level (P=0.005) and the ratio of MMP-9 to TIMP-1 expression (P=0.01) were significantly higher in the EP group than in the EN group. There was no significant difference in TGF-β mRNA expression between the two groups.
Sputum eosinophilia in patients with moderate-to-severe perennial rhinitis without AHR influenced FEV1 and the expression pattern of fibrosis-related mediators.
Sputum; eosinophil; rhinitis; forced expiratory volume; matrix metalloproteinase-9
The prevalence of bronchial hyperresponsiveness (BHR) to methacholine inhalation in a consecutive series of 21 patients with primary Sjögren's syndrome was studied prospectively. Slight to severe BHR was seen in 12/20 (60%) of the patients. Ten of 12 patients with BHR (83%) had a non-productive cough, wheezing, or intermittent breathlessness. Bronchial hyperresponsiveness was more common in patients with extraglandular symptoms (10/14, 71%) than in those with only glandular symptoms (29%). Spirometrically 29% (6/21) of the patients had 'small airways' disease', and all those had BHR. Of 6/21 (29%) who had diffuse interstitial lung disease, two had BHR. Three of the four patients with obstructive lung function were challenged with methacholine and two of them had BHR. Only two patients with BHR had normal spirometry findings. The data showed that respiratory disease--mostly mild or moderate but even severe bronchial hyperresponsiveness--is commonly seen in patients with primary Sjögren's syndrome.
Bronchial hyperresponsiveness (BHR) is a common feature of asthma. However, BHR is also present in asymptomatic individuals and its clinical and prognostic significance is unclear. We hypothesised that BHR might play a role in the development of chronic obstructive pulmonary disease (COPD) as well as asthma.
In 1991 respiratory symptoms and BHR to methacholine were evaluated in 7126 of the 9651 participants in the SAPALDIA cohort study. Eleven years later 5825 of these participants were re‐evaluated, of whom 4852 performed spirometric tests. COPD was defined as an FEV1/FVC ratio of <0.70.
In 1991 17% of participants had BHR, of whom 51% were asymptomatic. Eleven years later the prevalence of asthma, wheeze, and shortness of breath in formerly asymptomatic subjects with or without BHR was, respectively, 5.7% v 2.0%, 8.3% v 3.4%, and 19.1% v 11.9% (all p<0.001). Similar differences were observed for chronic cough (5.9% v 2.3%; p = 0.002) and COPD (37.9% v 14.3%; p<0.001). BHR conferred an adjusted odds ratio (OR) of 2.9 (95% CI 1.8 to 4.5) for wheezing at follow up among asymptomatic participants. The adjusted OR for COPD was 4.5 (95% CI 3.3 to 6.0). Silent BHR was associated with a significantly accelerated decline in FEV1 by 12 (5–18), 11 (5–16), and 4 (2–8) ml/year in current smokers, former smokers and never smokers, respectively, at SAPALDIA 2.
BHR is a risk factor for an accelerated decline in FEV1 and the development of asthma and COPD, irrespective of atopic status. Current smokers with BHR have a particularly high loss of FEV1.
bronchial hyperresponsiveness; asthma; chronic obstructive pulmonary disease; smoking; epidemiological study
The relationship between sensitisation to helminths and atopy, bronchial-hyperresponsiveness and allergic diseases may differ depending on many factors, including the genes of the population studied. We sought to examine this relationship in an African cohort.
Urban Xhosa children were tested for ascaris IgE levels, bronchial hyper-responsiveness (BHR) by methacholine challenge, atopic sensitisation (skin tests to aeroallergens) and allergic disease (asthma, eczema and rhinitis) assessed by questionnaire.
Ascaris sensitisation was strongly associated with BHR but not with asthma, eczema or rhinitis. There was a dose-response relationship between increasing class of ascaris IgE and increased BHR (Prevalence ratio (PR) 1.75; CI 1.09-2.82). Higher levels of ascaris IgE were seen in those with BHR. Ascaris IgE was associated with atopic sensitisation to aeroallergens. There was a dose-response relationship between increasing class of ascaris IgE and sensitisation to one or more allergen (PR 1.65; CI, 1.27-2.13), sensitisation to house dust mites (HDM) (PR 1.79; CI, 1.29-2.46) and grass (PR 2.66; CI, 1.24-5.71) and number of positive skin prick tests (PR 1.78; CI, 1.27-2.49). Presence of any sensitisation to ascaris was associated with more than doubling the prevalence of HDM sensitisation (41.5 vs 18.5%) and almost quadrupling the prevalence of grass sensitisation (10.8 vs 2.8%).
Ascaris sensitisation was strongly associated with BHR and with atopy, but not with allergic diseases. Possible explanations might be that the type of ascaris infection that causes high levels of ascaris IgE in this genetic population may also favour the development of atopy or that atopics in Africa have upregulation of their defence system against parasitic infection. These hypotheses are not mutually exclusive.
The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness
(BHR) that characterize asthma is achieved by the regulated accumulation and activation of
different leukocyte subsets in the lung. The development and maintenance of these processes
correlate with the coordinated production of chemokines. Here, we have assessed the role that
different chemokines play in lung allergic inflammation and BHR by blocking their activities
in vivo. Our results show that blockage of each one of these chemokines reduces both lung
leukocyte infiltration and BHR in a substantially different way. Thus, eotaxin neutralization reduces specifically BHR and lung eosinophilia transiently after each antigen exposure. Monocyte chemoattractant protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of inflammatory leukocytes in the airways, but rather by altering the trafficking of the
eosinophils and other leukocytes through the lung interstitium. Neutralization of RANTES
(regulated upon activation, normal T cell expressed and secreted) receptor(s) with a receptor
antagonist decreases significantly lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and RANTES. In contrast, neutralization of one of the ligands for RANTES receptors, macrophage-inflammatory protein 1α, reduces only slightly lung eosinophilia and BHR.
Finally, MCP-1 neutralization diminishes drastically BHR and inflammation, and this correlates
with a pronounced decrease in monocyte- and lymphocyte-derived inflammatory mediators.
These results suggest that different chemokines activate different cellular and molecular pathways
that in a coordinated fashion contribute to the complex pathophysiology of asthma, and that their
individual blockage results in intervention at different levels of these processes.
chemokines; allergic inflammation; bronchial hyperresponsiveness; eosinophilia; leukocytes
Asthma can be difficult to diagnose, but bronchial provocation with methacholine, exercise or mannitol is helpful when used to identify bronchial hyperresponsiveness (BHR), a key feature of the disease. The utility of these tests in subjects with signs and symptoms of asthma but without a clear diagnosis has not been investigated. We investigated the sensitivity and specificity of mannitol to identify exercise-induced bronchoconstriction (EIB) as a manifestation of BHR; compared this with methacholine; and compared the sensitivity and specificity of mannitol and methacholine for a clinician diagnosis of asthma.
509 people (6–50 yr) were enrolled, 78% were atopic, median FEV1 92.5% predicted, and a low NAEPPII asthma score of 1.2. Subjects with symptoms of seasonal allergy were excluded. BHR to exercise was defined as a ≥ 10% fall in FEV1 on at least one of two tests, to methacholine a PC20 ≤ 16 mg/ml and to mannitol a 15% fall in FEV1 at ≤ 635 mg or a 10% fall between doses. The clinician diagnosis of asthma was made on examination, history, skin tests, questionnaire and response to exercise but they were blind to the mannitol and methacholine results.
Mannitol and methacholine were therapeutically equivalent to identify EIB, a clinician diagnosis of asthma, and prevalence of BHR. The sensitivity/specificity of mannitol to identify EIB was 59%/65% and for methacholine it was 56%/69%. The BHR was mild. Mean EIB % fall in FEV1 in subjects positive to exercise was 19%, (SD 9.2), mannitol PD15 158 (CI:129,193) mg, and methacholine PC20 2.1(CI:1.7, 2.6)mg/ml. The prevalence of BHR was the same: for exercise (43.5%), mannitol (44.8%), and methacholine (41.6%) with a test agreement between 62 & 69%. The sensitivity and specificity for a clinician diagnosis of asthma was 56%/73% for mannitol and 51%/75% for methacholine. The sensitivity increased to 73% and 72% for mannitol and methacholine when two exercise tests were positive.
In this group with normal FEV1, mild symptoms, and mild BHR, the sensitivity and specificity for both mannitol and methacholine to identify EIB and a clinician diagnosis of asthma were equivalent, but lower than previously documented in well-defined populations.
This was a multi-center trial comprising 25 sites across the United States of America. (NCT0025229).
Gastroesophageal reflux disease (GERD) may cause, trigger or exacerbate many pulmonary diseases. The physiological link between GERD and pulmonary disease has been extensively studied in chronic cough and asthma. A primary care physician often encounters patients with extra esophageal manifestations of GERD in the absence of heartburn. Patients may present with symptoms involving the pulmonary system; noncardiac chest pain; and ear, nose and throat disorders. Local irritation in the esophagus can cause symptoms that vary from indigestion, like chest discomfort and abdominal pain, to coughing and wheezing. If the gastric acid reaches the back of the throat, it may cause a bitter taste in the mouth and/or aspiration of the gastric acid into the lungs. The acid can cause throat irritation, postnasal drip and hoarseness, as well as recurrent cough, chest congestion and lung inflammation leading to asthma and/or bronchitis/ pneumonia. This clinical review examines the potential pathophysiological mechanisms of pulmonary manifestations of GERD. It also reviews relevant clinical information concerning GERD-related chronic cough and asthma. Finally, a potential management strategy for GERD in pulmonary patients is discussed.
Gastroesophageal reflux disease; lungs; pulmonary
Perceived nasal and bronchial hyperresponsiveness to tobacco smoke and cold air were assessed in 912 working men in the Paris area. Baseline lung function measurements and peripheral leucocyte counts with standard differential counts were performed. At least one perceived nasal or bronchial hyperresponsiveness symptom was reported by 15.7%. Current smoking was significantly less frequent among those with cough induced by tobacco smoke. Rhinitis induced by cold air was associated with lower FEV1 (p less than 0.01) and the association remained after adjustment for smoking, asthma, and wheezing (p = 0.06). Symptoms induced by cold air were related to circulating basophils. Neither perceived nasal nor perceived bronchial hyperresponsiveness was significantly related to the airway response to methacholine in a sample of the group (n = 324) surveyed again five years later. The result suggest that the symptom of rhinitis provoked by cold air is a possible "new" risk factor or marker for chronic airflow limitation.
Cough is one of the most common complaints for which patients seek medical attention. Misdiagnosis and mistreatment of cough exist commonly in China. The prevalence of acute cough caused by upper airway infection fluctuates between 9% and 64% in the community, for chronic cough, the prevalence >10% in most surveys, ranging from 7.2%-33%. The common causes of chronic cough are upper airway cough syndrome (previously called as post nasal drip syndrome [PNDS]), cough variant asthma (CVA), gastroesophageal reflux related cough (GERD) and eosinophilic bronchitis (EB). There is a regional discrepancy regarding the prevalence of common causes of cough and distribution of gender among China, UK, USA, the most common cause of chronic cough in China are CVA, followed by UACS, EB and atopic cough (AC), the male is almost equal to female in numbers in China. The risk factors for cough includes cold air, smoking, environmental pollutants, noxious substances and allergens, and unreasonable diet habits.
Cough; Epidemiology; Etiology; Risk factor; Quality of life
Allergic rhinitis is a highly prevalent condition, particularly among children, whose schoolwork and quality of life may be impaired by its symptoms.
In this prospective, multicenter study, children between 6 and 12 years old with a diagnosis of severe perennial allergic rhinitis received a combination of the nonsedating antihistamine loratadine and the corticosteroid betamethasone in an oral solution for 5 days.
The total nasal and ocular symptom score was significantly reduced from 11.4 (± 2.1) before treatment to 2.9 (± 2.4) after treatment (P < 0.01). Significant reductions (P < 0.01) were also observed for sneezing, nasal pruritus, nasal congestion, rhinorrhea, postnasal drip, and ocular erythema and pruritus. No adverse events were reported, and no subject discontinued treatment.
The combination of loratadine and betamethasone in an oral solution was safe and effective as initial short-term treatment for symptoms of severe perennial allergic rhinitis in school-aged children.
etamethasone; loratadine; pediatric; perennial allergic rhinitis; quality of life
The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium.
Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles.
This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls). The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used.
The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions.
Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be potential targets for future drug development.
The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction.
Rhinitis is characterized by rhinorrhea, sneezing, nasal congestion, nasal itch and/or postnasal drip. Often the first step in arriving at a diagnosis is to exclude or diagnose sensitivity to inhalant allergens. Non-allergic rhinitis (NAR) comprises multiple distinct conditions that may even co-exist with allergic rhinitis (AR). They may differ in their presentation and treatment. As well, the pathogenesis of NAR is not clearly elucidated and likely varied. There are many conditions that can have similar presentations to NAR or AR, including nasal polyps, anatomical/mechanical factors, autoimmune diseases, metabolic conditions, genetic conditions and immunodeficiency. Here we present a case of a rare condition initially diagnosed and treated as typical allergic rhinitis vs. vasomotor rhinitis, but found to be something much more serious. This case illustrates the importance of maintaining an appropriate differential diagnosis for a complaint routinely seen as mundane. The case presentation is followed by a review of the potential causes and pathogenesis of NAR.
Background: Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks.
Methods: Twenty six asthmatic patients aged 21–59 years were selected for this randomised, double blind, parallel group study. The effect of 250 µg inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV1) by 15% (PD15FEV1) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD15FEV1 were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves.
Results: The increase in PD15FEV1 from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD15FEV1 was 1.85–2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment.
Conclusions: A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 µg. The effect tapered within 2 weeks of cessation of treatment.
Bronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5'-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma.
The medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed.
The concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r2=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively).
Our results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.
AMP; atopic asthma; bronchial hyper-responsiveness; methacholine