United Airway Research Articles

The functional connection between oral allergy syndrome and united airways disease assessed by oral challenge

BackgroundThe airways and the upper digestive tract have a common embryonic origin. In sensitized subjects they can respond to allergens with an immediate reaction (asthma, rhinitis, or oral allergy syndrome [OAS]). ObjectiveTo investigate the possible functional connection between respiratory and upper digestive tract by means of specific oral allergen challenges. MethodsPatients sensitized to birch and apple were subdivided into group A (n = 12; asthma + rhinitis caused by birch and OAS caused by apple); group B (n = 10; OAS caused by apple without asthma/rhinitis); group C (n = 8; asthma and rhinitis caused by birch without OAS). Healthy subjects represented the control group D (n = 6). Oral provocation test with apple was performed out of the pollen season. Visual analog scale for eye, nose, and mouth symptoms, spirometry, nasal eosinophil count, and exhaled nitric oxide were assessed before and 6 hours after challenge. ResultsNo change occurred in nasal and ocular symptoms before versus after challenge in all groups. On the contrary, in groups A and B the oral scores significantly increased after challenge (P < .001), whereas no change was seen in groups C and D. Exhaled nitric oxide and nasal eosinophils showed no change before versus after challenge in all groups. Nitric oxide was higher before and after challenge in groups A and C vs groups B and D. No change was seen in either forced vital capacity or forced expiratory volume in 1 second. ConclusionIn the case of birch-apple syndrome, eating apple does not functionally or clinically affect the respiratory tract.

Is There an Association Between Otitis Media and Nasal Polyposis?

The association between otitis media with effusion (OME) and nasal polyposis (NP) is poorly described. However, two different approaches to this problem seem to come from the few studies concerning both otitis media and NP in the literature. One study was based on the assessment of a population of patients presenting with NP, with the authors interested in patients among the studied population who complained of ear-related symptoms and developed OME (rhinologic approach). Other studies were based on the assessment of a population of patients developing a particular OME, with the authors interested in characterizing this condition they named eosinophilic otitis media (otologic approach). The article reviews currents concepts in the relationship between OME and NP. It appears that regardless of the approach to the problem of interest (rhinologic or otologic approach), OME and NP seem to be closely related. Moreover, some striking similarities can be noted between the different entities described in the different studies reviewed, and all authors seem to agree that the middle ear has a central role in the concept of united airways inflammatory disease. Otologists and rhinologists should work together on a single approach that allows for better management of inflammatory disease leading to the formation of polyps, development of concurrent asthma, appearance of aspirin intolerance, and finally involvement of the middle ear.

United airways disease among florists

Previously we observed an excess risk for occupational asthma among florists with rhinitis. To further evaluate the link between upper and lower airways, we investigated &lt;em&gt;united airways disease&lt;/em&gt; in the same occupational group. Occupational history, symptoms and atopy were investigated among 128 florists. Age-, smoking-, and gender-adjusted risks were calculated using logistic regression models comparing symptomatic and asymptomatic individuals. The prevalence of work-related rhinitis symptoms was 13.3%, conjunctivitis symptoms and asthma-like symptoms were 14.1%. We observed an excess risk of work-related asthma symptoms among florists with work-related conjunctivitis (OR: 8.5, 95% CI: 2.4-29.9) and rhinitis (OR: 13.1, 95% CI: 3.0- 58.0). Florists with positive allergen skin test for flower mix were 13.0 times more likely to have work-related rhinitis and 12.5 times more likely to have work-related conjunctivitis. The observed relationship between work-related asthma and rhinoconjunctivitis is supportive of the concept of the &lt;em&gt;united airways disease&lt;/em&gt;.

United airways disease among florists

Previously we observed an excess risk for occupational asthma among florists with rhinitis. To further evaluate the link between upper and lower airways, we investigated united airways disease in the same occupational group. Occupational history, symptoms and atopy were investigated among 128 florists. Age-, smoking-, and gender-adjusted risks were calculated using logistic regression models comparing symptomatic and asymptomatic individuals. The prevalence of work-related rhinitis symptoms was 13.3%, conjunctivitis symptoms and asthma-like symptoms were 14.1%. We observed an excess risk of work-related asthma symptoms among florists with work-related conjunctivitis (OR: 8.5, 95% CI: 2.4-29.9) and rhinitis (OR: 13.1, 95% CI: 3.0- 58.0). Florists with positive allergen skin test for flower mix were 13.0 times more likely to have work-related rhinitis and 12.5 times more likely to have work-related conjunctivitis. The observed relationship between work-related asthma and rhinoconjunctivitis is supportive of the concept of the united airways disease.

Symptoms and Signs from the Nose and Sinuses in Asthmatics

Objective: The United Airways Disease hypothesis suggests a link between upper and lower airways in asthmatics. However, there is a need to know more about nose and sinus related quality of life, sinonasal symptoms, and objective nasal air flow in asthmatics compared with healthy individuals. Method: One hundred asthmatics and 96 nonasthmatic controls underwent a prospective controlled survey from June 2009 to December 2010. Symptoms, quality of life, and nasal airflow were assessed on Visual Analogue Scales (VAS, 0-100), Sino-Nasal-Outcome-Test (SNOT-20), and Peak Nasal Inspiratory Flow (PNIF), respectively. Results: Asthmatics (male/female 41/59; mean age, 44.1 years; range, 19-64 years) reported significantly more symptoms of nasal obstruction [mean VAS 38mm (SD 26) vs 9 mm (SD 12), P &lt; .001] than controls (male/female 43/53; mean age, 41 years; range, 20-65 years). PNIF was significantly lower in asthmatics than controls [mean PNIF 85 l/min (SD 24) vs 102 l/min (SD 19), P &lt; .001]. Conclusion: This study provides further evidence of the clinical importance of the upper airway in the diagnostic and therapeutic management of asthmatic patients.

Chronic rhinosinusitis, nasal polyposis and asthma: the united airways concept reconsidered?

Cite this as: G.‐J. Braunstahl, Clinical &amp; Experimental Allergy, 2011 (41) 1341–1343.

Nasal Eosinophilia can Predict Bronchial Hyperresponsiveness in Persistent Rhinitis: Evidence for United Airways Disease Concept

Nasal eosinophils may be indicative of bronchial hyperresponsiveness (BHR) in rhinitis concerning the "united airways disease" theory. This study was designed to evaluate the relationship between nasal eosinophilia and BHR in persistent perennial rhinitis patients. Thirty-seven patients (12 males and 25 females, mean age: 33.3 ± 10.4 years) were included in the study. Skin-prick test, nasal symptom score, nasal smears, methacholine bronchial challenge test, and nasal rhinometry were obtained in all patients. Eosinophil count in nasal smears was expressed as a percentage of the total cells. None of the patients had asthma. There was no difference between the number of atopic and nonatopic patients having BHR (4/20 versus 4/17; chi-squared = 0.07; p > 0.05). Total nasal flow was lower and percentage of nasal eosinophils was higher in the patients with BHR than in patients without BHR (p = 0.012 and p = 0.009, respectively). A cutoff point of 68% nasal eosinophils yielded a sensitivity of 100% (63.1-100) and a specificity of 58.6% (38.9-76.5) to determine the presence of BHR. Positive likelihood ratio for the value of eosinophils above cutoff value was 2.42 (1.8-3.3). This study shows the relationship between nasal eosinophils and BHR in persistent perennial rhinitis patients. Nasal eosinophil percentage below cutoff value indicates that a patient does not have BHR.

The Frequency of Chronic Rhinosinusitis/Nasal Polyp in COPD and Its Effect on the Severity of COPD

This study aimed to investigate the effect of chronic rhinosinusitis/nasal polyposis on the severity of COPD and to find out whether the ‘united airway disease’ hypothesis is valid for COPD. The study enrolled 90 patients diagnosed and staged according to criteria of an international guideline for diagnosis and management of COPD. The patients in stages I and II were classified as Group 1 and the patients in stages III and IV as Group 2. All the patients were questioned about the presence of major and minor criteria of sinusitis, underwent paranasal sinus computed tomography (PNS-CT) scans, and answered a questionnaire based on a quality of life test for sinusitis (SNOT-20). Sinusitis was present in 48 (53%) patients according to criteria of major and minor symptoms, and in 58 (64%) patients according to Lund-Mackay scoring system of PNS-CT. There was no significant difference in CT score between Group 1 and Group 2 (2.3 ± 0.5 vs. 2.1 ± 0.4, p > 0.05). However, the frequency of minor symptoms was greater in Group 2. SNOT-20 score was significantly higher in Group 2 than in Group 1 (28.7 ± 1.7 and 22.2 ± 1.9, respectively, p = 0.014). A significant correlation was determined between Lund-Mackay and SNOT-20 scores. The presence of CRS should be assessed in COPD patients, especially in those with severe disease. Further research is needed to disclose possible common immunopathological mechanisms in the pathogeneses of COPD and CRS.

Oral Allergy Syndrome and United Airways Disease. Is there a functional connection?

Oral Allergy Syndrome and United Airways Disease. Is there a functional connection?

Nonallergic Rhinitis and its Association with Smoking and Lower Airway Disease: A General Population Study

The cause of nonallergic rhinitis (NAR) and its relation to lower airway disease remains unclear. The purpose of this study was to perform a descriptive analysis of the occurrence of rhinitis in a Danish general population with focus on NAR and its association with smoking and lower airway disease. A population-based, cross-sectional study conducted in Copenhagen, Denmark was performed. A random sample from the general population (n = 7931; age, 18-69 years) was invited to a general health examination including measurements of serum-specific immunoglobulin E (IgE) to common aeroallergens; 3471 (44%) persons were accepted. For further analysis, we divided the population into the following groups: (I) negative specific IgE and no rhinitis (controls); (II) negative specific IgE and rhinitis (NAR); (III) positive specific IgE and rhinitis (allergic rhinitis [AR]); and (IV) positive specific IgE but no rhinitis (sensitized). We found that NAR was associated with asthma (odds ratio [OR] = 2.51 [1.87-3.37]); chronic bronchitis (OR = 2.27 [1.85-2.79]); current smoking (>15 g/day; OR = 1.57 [1.18-2.08]); lower forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratios and reduced FEV(1) values. The association with chronic bronchitis was stronger in NAR than in AR, whereas the opposite was true for asthma. FEV(1)/FVC of <70% was not significantly associated to any group. This epidemiological study indicates that both asthma and chronic bronchitis are important comorbidities in NAR confirming the "united airway" hypothesis, and that smoking might be a significant modulator of disease. Although NAR was significantly associated with poor lung function, no significant association with chronic obstructive pulmonary disease was shown.

Preventing progression of allergic rhinitis: the role of specific immunotherapy

Allergic rhinitis and asthma are examples of allergic airways disease. Despite their differing symptomatology, both disorders affect the mucosal lining of the respiratory tract and are linked by common underlying...

Relationship between Olfactory Acuity and Peak Expiratory Flow during Postoperative Follow-up in Chronic Rhinosinusitis Associated with Asthma

The link between nasal and bronchial disease has been studied extensively for chronic rhinosinusitis and asthma. The concept of "united airway allergy" has become widely accepted in the past decade. We evaluated the relationship between the upper and lower airways during follow-up after endoscopic sinus surgery by monitoring sinonasal and pulmonary functions. Thirty-nine subjects with chronic rhinosinusitis associated with bronchial asthma were entered in this study. A self smell test using stick-type odorant materials was carried out daily to evaluate postoperative recurrence of sinonasal disease. Each patient was assessed for peak expiratory flow (PEF) 3 times daily. The average (+/- SD) scores of initial symptoms were 8.3 +/- 2.2, which was significantly decreased to 1.5 +/- 1.4 by 3 months after operation. During postoperative follow-up, 25 of 39 patients showed no decrease in PEF, whereas the other 14 patients had at least 1 episode of a significant decline in PEF. In the postoperative course, with respect to the self smell test, 24 patients showed no aggravation of smell, but 15 patients had episode(s) of decreased olfaction. Twelve patients demonstrated worsening on the smell test concomitant with a decreased PEF. A discrepancy between olfactory acuity and pulmonary function was recognized in 5 patients. There were 22 patients with a good prognosis of parameters of both the upper and lower airways. Daily monitoring of both upper and lower respiratory tract functions clearly revealed dual relationships, indicating that worsening of sinusitis accompanies asthma exacerbation. Appropriate measures of the upper and lower airways following endoscopic sinus surgery can be used to predict patient outcome.

Novel Perspectives in the Detection of Oral and Nasal Oxidative Stress and Inflammation in Pediatric United Airway Diseases

United airway disease (UAD) concept proposed that asthma and rhinitis are both different clinical manifestation of a single inflammatory process. The aim of this study is to assess in upper and lower airways the level of inflammation and oxidative stress and to investigate the relationship between biomarkers in persistent allergic rhinitis (PER) and in concomitant asthma with PER. By a crosssectional study we measured oral and nasal (FENO) and oral and nasal EBC 8-isoprostane, LTB4 and PGE2 in children with PER (n=14) and with PER and concomitant intermittent asthma (IA; n=25), mild persistent asthma (mA; n=28), moderate persistent asthma (MA; n=13) and in Healthy Controls (HCs; n=13). Oral and nasal FENO concentrations were increased in children with PER, IA, mA and MA when compared with HCs. Nasal 8-isoprostane was higher in EBC of children with PER and asthma than in HCs. Oral and nasal LTB4 were higher in EBC of children with PER and mA than in HCs. Oral and nasal PGE2 concentrations were higher in EBC of children with PER than in HCs. Positive correlations between oral and nasal biomarkers were found in IA for LTB4 and PGE2, in mA for FENO, 8-isoprostane, LTB4 and PGE2, and in MA for PGE2. No correlations were observed in children with PER and HCs. Our results suggest that non-invasive markers of inflammation and oxidative stress might be useful to study the relationships between oral and nasal compartments in allergic children with PER and concomitant asthma with the aim of defining the UAD.

A related heredity epidemiological research on allergic rhinitis and asthma in Nantong region

To discuss the related impact of genetic factors in the incidence of bronchial asthma (BA) and allergic rhinitis (AR) in Nantong region, China. By random sampling method, investigation and research on the incidence of genetic epidemiology were carried out in the population of 95 300 on AR and BA. The rate of patients with allergic rhinitis with asthma was 25.92% (296/1142), the rate of asthma patients with allergic rhinitis was 40.49% (296/731). The prevalences of AR complicated with BA were 8.19% (280/3418), 3.08% (154/5002) and 3.16% (85/2687) in the first-, second-and third-degree relatives of the probands respectively, while the prevalences of BA complicated with AR were 15.81% (466/2947), 4.61% (229/4967) and 2.51% (134/5345) in the first-, second- and third-degree relatives of the probands respectively, higher than those in the controls (P < 0.05). The weighted mean heritability of AR in BA patients was 94.2% ± 1.9%, while the weighted mean heritability of BA in AR patients was 81.8% ± 2.1%, more than 60%, suggesting that both AR and BA were relevant with genetics. The incidence of BA and AR has obvious relevance, supporting the theory that the two diseases are an united airway disease and relevant with polygene heredity.

Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis

The relationships between asthma and rhinitis are still a crucial point in respiratory allergy and have scarcely been analysed in occupational setting. We aimed to compare the clinical and inflammatory features of subjects with occupational asthma only (OA) to subjects with OA associated to occupational rhinitis (OAR) caused by persulphate salts. The clinical charts of 26 subjects diagnosed in our Unit as respiratory allergy caused by ammonium persulphate (AP), confirmed by specific inhalation challenge (SIC), were reviewed. Twenty-two out of twenty-six patients underwent pre-SIC-induced sputum challenge test (IS) and 24/26 underwent nasal secretion collection and processing. Twelve out of twenty-six patients received a diagnosis of OA-only and 14/26 of OAR. Duration of exposure before diagnosis, latency period between the beginning of exposure and asthma symptom onset, basal FEV(1), airway reactivity to methacholine and asthma severity did not differ in the two groups. Eosinophilic inflammation of upper and lower airways characterized both groups. Eosinophil percentage in IS tended to be higher in OAR [11.9 (5.575-13.925)%] than in OA-only [2.95 (0.225-12.5)%] (P = 0.31). Eosinophilia in nasal secretions was present both in subjects with OAR [55 (46-71)%] and in subjects with OA-only [38 (15-73.5)%], without any significant difference. Our results indicate that OA because of ammonium persulphate coexists with occupational rhinitis in half of the patients. Unexpectedly, rhinitis did not seem to have an impact on the natural history of asthma. The finding of nasal inflammation in subjects with OA-only without clinical manifestations of rhinitis supports the united airway disease concept in occupational respiratory allergy as a result of persulphates.

The link between allergic rhinitis and asthma: the united airways disease

Rhinitis and asthma are often associated and the two disorders interact at various levels. Rhinitis typically precedes the development of asthma and can contribute to unsatisfactory asthma control. The presence and type of asthma is influenced by sensitization, and the duration and severity of allergic rhinitis. Nasal symptoms, airflow and markers of inflammation directly correlate with lower airway involvement. Local tissue factors, such as microbial stimuli and systemic inflammatory mechanisms, play a role in the clinical expression of the allergic airway syndrome. There is increasing evidence that suggests a major involvement of airway epithelial cells in the pathogenesis of both asthma and allergic rhinitis. Even in patients with rhinitis who do not have asthma, subclinical changes in the lower airways and inflammatory mediators can be detected. The pathogenic role of paranasal sinus infections in respiratory allergy has been better elucidated but there remains a need for further research. Treatment of established rhinitis may affect asthma control and could have some impact on airway obstruction, but a direct effect of rhinitis therapy on lower airway inflammation remains to be clearly established.

Noninvasive methods for assessment of airway inflammation in occupational settings

The present document is a consensus statement reached by a panel of experts on noninvasive methods for assessment of airway inflammation in the investigation of occupational respiratory diseases, such as occupational rhinitis, occupational asthma, and nonasthmatic eosinophilic bronchitis. Both the upper and the lower airway inflammation have been reviewed and appraised reinforcing the concept of 'united airway disease' in the occupational settings. The most widely used noninvasive methods to assess bronchial inflammation are covered: induced sputum, fractional exhaled nitric oxide (FeNO) concentration, and exhaled breath condensate. Nasal inflammation may be assessed by noninvasive approaches such as nasal cytology and nasal lavage, which provide information on different aspects of inflammatory processes (cellular vs mediators). Key messages and suggestions on the use of noninvasive methods for assessment of airway inflammation in the investigation and diagnosis of occupational airway diseases are issued.

United airways: circulating Th2 effector cells in an allergic rhinitis model are responsible for promoting lower airways inflammation

Allergic rhinitis (AR) and asthma often coexist and are referred to as 'united airways' disease. However, the molecular and cellular pathways that are crucially involved in the interaction between upper and lower airways remain to be identified. We sought to assess whether and how AR exacerbates lower airway inflammation upon allergen challenge in mice. We previously developed an intranasal ovalbumin (OVA)-driven AR model, characterized by nasal eosinophilic inflammation, enhanced serum levels of OVA-specific IgE and Th2 cytokine production in cervical lymph nodes. In OVA-sensitized mice with or without AR, a lower airway challenge was given, and after 24 h, lower airway inflammation was analysed. We found that AR mice were more susceptible to eosinophilic inflammation following a lower airway OVA challenge than OVA-sensitized controls. AR mice manifested increased numbers of eosinophils in bronchoalveolar lavage fluid and increased inter-cellular adhesion molecule-1 (ICAM-1) expression on lung endothelium, when compared with OVA-sensitized controls. Depletion of T cells in OVA-challenged AR mice completely abrogated all hallmarks of lower airway inflammation, including enhanced IL-5 and tissue eosinophilia. Conversely, adoptive transfer of Th2 effector cells in naïve animals induced lower airway eosinophilic inflammation after challenge with OVA. Blocking T cell recirculation during AR development by the spingosine-1 analogue FTY720 also prevented lower airway inflammation including ICAM-1 expression in AR mice upon a single lower airway challenge. Our mouse model of 'united airways' disease supports epidemiological and clinical data that AR has a significant impact on lower airway inflammation. Circulating Th2 effector cells are responsible for lung priming in AR mice, most likely through up-regulation of ICAM-1.

Asthma and rhinoconjunctivitis comorbidity: United airway disease or inherited target organs?

The idea of a united airway disease for asthma and rhinoconjunctivitis is supported by clinical and epidemiological data. However, many asthmatics do not have rhinoconjunctivitis and vice versa. The aim of this study was to investigate if the family history of a specific organ involvement is associated with the implication of the same organ in the allergic child. According to the organ involvement in either or both parents, the family history of 739 children who were skin prick positive to either Dermatophagoides pteronyssinus or D. farinae or both was defined as: asthma and rhinoconjunctivitis positive; asthma and rhinoconjunctivitis negative; asthma negative and rhinoconjunctivitis positive; and asthma positive and rhinoconjunctivitis negative. Asthma and rhinoconjunctivitis in the children were defined according to the International Study of Asthma and Allergies in Childhood questionnaire. Associations between each type of family history and the presence of asthma and/or rhinoconjunctivitis in the children were calculated and adjusted for usual confounders. Adjusted odds ratio of children having asthma, when family history included asthma, was 2.48 (1.38-4.45) when it also included rhinoconjunctivitis; and 2.13 (1.12-4.05) when it did not. However, family history of rhinoconjunctivitis was not associated with asthma in the child. Conversely, the odds ratio of children having rhinoconjunctivitis when family history included rhinoconjunctivitis was 1.84 (1.05-3.21) when it also included asthma; and 1.89 (1.23-2.89) when it did not. Family history of asthma was not associated with rhinoconjunctivitis in the child. In a population of children sensitized to mites, the organ or organs (nose and/or lung) which are implicated in parents tend to be also involved in their children.

United Airways Concept: What Does it Teach Us about Systemic Inflammation in Airways Disease?

Allergic asthma and rhinitis are manifestations of the atopic syndrome and often coexist. It has been demonstrated that allergic rhinitis is a strong risk factor for the onset of asthma in adults. Genetic and environmental factors are recognized as contributing factors to the development of the allergic airway syndrome. Insight in the risk factors responsible for allergic airways disease and the interaction between the involved organs results in a better understanding and treatment of the syndrome. Several mechanisms have been proposed for the interaction between upper and lower airways in allergic rhinitis and asthma. It has been clearly shown in many studies that impaired nasal function affects the lower airways of patients with asthma. The evidence for aspiration of nasal contents or neural reflexes as an explanation for nasobronchial cross-talk is lacking. To date, most human and animal data point toward a systemic pathway linking the upper and lower airways, involving both bloodstream and bone marrow. Serum IL-5 and blood eosinophils are increased as well as adhesion molecule expression after local allergen challenge. Moreover, mucosal inflammation was not restricted to the challenged organ only, but extended throughout the whole airway in subjects with allergic rhinitis. Nasobronchial interaction in allergic airway disease has profound impact on daily clinic. Nasal therapy in allergic rhinitis patients with asthma has a beneficial effect on asthma symptoms, bronchial hyperresponsiveness, and airway inflammation. Furthermore, it reduces the risk of asthma exacerbations. It stresses the importance of an integrated therapeutic approach involving both ends of the respiratory tract.