Eicosanoids seasonally impact pulmonary function in asthmatic patients with Japanese cedar pollinosis.

BACKGROUND: Condition of asthma in patients with asthma and concomitant seasonal allergic rhinitis (SAR) deteriorates during the Japanese cedar pollen (JCP) season. However, the underlying mechanisms remain unclear. METHODS: We analyzed seasonal variations in eicosanoid levels in the airways of patients with asthma and concomitant SAR sensitized to JCP (N = 29, BA-SAR-JCP group) and those not sensitized (N = 13, BA-AR-non-JCP group) during the JCP season. The association between changes in eicosanoid concentrations and pulmonary function was assessed. Exhaled breath condensate (EBC) was collected, and pulmonary function tests were performed during the JCP and non-JCP seasons. The cysteinyl leukotriene (CysLT), thromboxane B2 (TXB2), prostaglandin D2-methoxime (PGD2-MOX), and leukotriene B4 (LTB4) levels in the collected EBC were measured via enzyme-linked immunosorbent immunoassays. RESULTS: The log CysLT levels significantly increased in the BA-SAR-JCP group during the JCP season compared with the non-JCP season (1.78 ± 0.55, 1.39 ± 0.63 pg/mL, mean ± standard deviation, respectively, p = 0.01) and those in the BA-AR-non-JCP group during the JCP season (1.39 ± 0.38 pg/mL, p = 0.04). Moreover, the log TXB2 levels seemed to increase. However, the log LTB4 and log PGD2-MOX levels did not increase. The changes in the log CysLT levels during the two seasons were negatively correlated to forced expiratory volume in one second (FEV1) in the BA-SAR-JCP group (r = -0.52, p < 0.01). CONCLUSIONS: In the BA-SAR-JCP group, seasonal increases in eicosanoid levels in the airway likely promoted deterioration in pulmonary function despite optimal maintenance treatment.

Analysis of the Serum Cytokine Profile in Allergic Patients Opens a Way to Personalized Treatment of Allergy.

Plant lipid transfer proteins and homologues of the main birch pollen allergen Bet v 1 are involved in the development of allergic reactions of varying severity to plant foods and pollen. In this study, the sera from patients with tree and weed pollen allergies in the Moscow region were examined. The levels of IL-4, IL-5, IL-9, IL-10, IL-13, IL-17A, IFNγ, TNFα, and TNFß cytokines were determined in the sera of patients with specific IgE antibodies to Bet v 1 and Pru p 3 allergens. It was confirmed that patients with pollen allergy are often characterized by Th2 response of the immune system, though other mechanisms of allergy development occurred in some cases. The data obtained demonstrate the necessity of detailed analysis of the individual mechanism of allergic reactions and patient-centered approach to the personalized allergy treatment.

Evidence of fatigue, disordered sleep and peripheral inflammation, but not increased brain TSPO expression, in seasonal allergy: A [11C]PBR28 PET study.

Allergy is associated with non-specific symptoms such as fatigue, sleep problems and impaired cognition. One explanation could be that the allergic inflammatory state includes activation of immune cells in the brain, but this hypothesis has not been tested in humans. The aim of the present study was therefore to investigate seasonal changes in the glial cell marker translocator protein (TSPO), and to relate this to peripheral inflammation, fatigue and sleep, in allergy. We examined 18 patients with severe seasonal allergy, and 13 healthy subjects in and out-of pollen season using positron emission tomography (n = 15/13) and the TSPO radioligand [11C]PBR28. In addition, TNF-α, IL-5, IL-6, IL-8 and IFN-γ were measured in peripheral blood, and subjective ratings of fatigue and sleepiness as well as objective and subjective sleep were investigated. No difference in levels of TSPO was seen between patients and healthy subjects, nor in relation to pollen season. However, allergic subjects displayed both increased fatigue, sleepiness and increased percentage of deep sleep, as well as increased levels of IL-5 and TNF-α during pollen season, compared to healthy subjects. Allergic subjects also had shorter total sleep time, regardless of season. In conclusion, allergic subjects are indicated to respond to allergen exposure during pollen season with a clear pattern of behavioral disruption and peripheral inflammatory activation, but not with changes in brain TSPO levels. This underscores a need for development and use of more specific markers to understand brain consequences of peripheral inflammation that will be applicable in human subjects.

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or ß-estimates with 95% confidence interval (CI). RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: ß=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: ß=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2 higher BMI. CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

The TLR4-TRIF pathway can protect against the development of experimental allergic asthma.

The Toll-like receptor (TLR) adaptor proteins myeloid differentiating factor 88 (MyD88) and Toll, interleukin-1 receptor and resistance protein (TIR) domain-containing adaptor inducing interferon-ß (TRIF) comprise the two principal limbs of the TLR signalling network. We studied the role of these adaptors in the TLR4-dependent inhibition of allergic airway disease and induction of CD4+ ICOS+ T cells by nasal application of Protollin™, a mucosal adjuvant composed of TLR2 and TLR4 agonists. Wild-type (WT), Trif-/- or Myd88-/- mice were sensitized to birch pollen extract (BPEx), then received intranasal Protollin followed by consecutive BPEx challenges. Protollin's protection against allergic airway disease was TRIF-dependent and MyD88-independent. TRIF deficiency diminished the CD4+ ICOS+ T-cell subsets in the lymph nodes draining the nasal mucosa, as well as their recruitment to the lungs. Overall, TRIF deficiency reduced the proportion of cervical lymph node and lung CD4+ ICOS+ Foxp3- cells, in particular. Adoptive transfer of cervical lymph node cells supported a role for Protollin-induced CD4+ ICOS+ cells in the TRIF-dependent inhibition of airway hyper-responsiveness. Hence, our data demonstrate that stimulation of the TLR4-TRIF pathway can protect against the development of allergic airway disease and that a TRIF-dependent adjuvant effect on CD4+ ICOS+ T-cell responses may be a contributing mechanism.

Allergic Rhinitis.

Among the atopic disorders, allergic rhinitis is the most prevalent. Patients who suffer from allergic rhinitis sustain significant morbidity and loss of productivity. Cardinal symptoms include nasal congestion, rhinorrhea, sneezing, and nasal itching, although multiple related symptoms may occur. Causes should be ruled out with a thorough history and physical examination, with particular attention to red flag or atypical symptoms. Skin testing or serum sampling can confirm diagnosis and also guide therapy. Therapy is multimodal, tailored to a particular patient's symptom burden and quality of life.

Cockroach sensitization mitigates allergic rhinoconjunctivitis symptom severity in patients allergic to house dust mites and pollen.

BACKGROUND: Modifiers of symptom severity in patients with allergic rhinoconjunctivitis (AR) are imprecisely characterized. The hygiene hypothesis implicates childhood microbial exposure as a protective factor. Cockroach sensitization (C+) might be a proxy for microbial exposure. OBJECTIVE: We sought to determine whether C+ assayed by means of skin prick tests influenced AR symptom severity in controlled and natural settings. METHODS: Total symptom scores (TSSs) were recorded by 21 participants with house dust mite allergy (M+) in the natural setting and during repeated exposures of 3 hours per day to house dust mite allergen in an allergen challenge chamber (ACC). In M+ participants the peripheral blood and nasal cells were assayed for T-cell activation and transcriptomic profiles (by using RNA sequencing), respectively. Participants allergic to mountain cedar (n = 21), oak (n = 34), and ragweed (n = 23) recorded TSSs during separate out-of-season exposures to these pollens (any pollen sensitization [P+]) in the ACC; a subset recorded TSSs in the pollination seasons. RESULTS: The hierarchy of TSSs (highest to lowest) among M+ participants tracked the following skin prick test sensitization statuses: M+P+C- > M+P+C+ > M+P-C- > M+P-C+. In nasal cells and peripheral blood the immune/inflammatory responses were rapidly resolved in M+P+C+ compared with M+P+C- participants. Among those allergic to pollen, C+ was associated with a lower TSS during pollen challenges and the pollination season. After aggregated analysis of all 4 ACC studies, C+ status was associated with a 2.8-fold greater likelihood of a lower TSS compared with C- status (odds ratio, 2.78; 95% CI, 1.18-6.67; P = .02). CONCLUSIONS: C+ status is associated with mitigation of AR symptom severity in adults with AR.

Hormonal factors and incident asthma and allergic rhinitis during puberty in girls.

BACKGROUND: Accumulating evidence is indicating that hormonal factors play a role in new-onset allergic rhinitis and asthma after puberty. OBJECTIVE: To determine whether age at menarche and use of hormonal contraceptives predict new-onset allergic rhinitis and asthma after puberty in young German women. METHODS: A prospective community-based cohort study followed 1,191 girls 9 to 11 years old to early adulthood (19-24 years old). Self-administrated questionnaires concerning age at menarche, use of hormonal contraceptives, and status and age at onset of physician-diagnosed allergic rhinitis and asthma were collected at 16 to 18 and 19 to 24 years of age. Logistic regression models were used to analyze the incidence of asthma and allergic rhinitis after puberty and pooled estimates were obtained from the final model. RESULTS: Eleven percent of girls developed allergic rhinitis after menarche and 3% reported new-onset asthma. Late menarche (>13 years of age) was statistically significantly inversely related to allergic rhinitis (adjusted odds ratio [OR] 0.32, 95% confidence interval [CI] 0.14-0.74) but did not reach the level of statistical significance for asthma (OR 0.32, 95% CI 0.07-1.42). Use of hormonal contraceptives was inversely associated with new-onset allergic rhinitis (OR 0.14, 95% CI 0.08-0.23) and asthma (OR 0.27, 95% CI 0.12-0.58) after puberty. CONCLUSION: This study shows that girls with late onset of menarche are less likely to develop allergic rhinitis after puberty compared with those who have menarche at an average age. These findings also suggest that, in addition to endogenous hormones, hormonal contraceptives play a role and might protect young women from allergies and asthma.

Examining impacts of allergic diseases on psychological problems and tobacco use in Korean adolescents: the 2008-2011 Korean National Health and Nutrition Examination Survey.

PURPOSE: Asthma during adolescence can induce social, psychological, and behavioral problems. We examined the impact of asthma and other allergic diseases on psychological symptoms and health risk behaviors among South Korean adolescents. METHODS: In this population-based cross-sectional study, 3192 adolescents (10-18 years of age) participating in the 2008-2011 Korean National Health and Nutrition Examination Survey were enrolled. Psychological problems associated with clinically diagnosed asthma, allergic rhinitis, and atopic dermatitis were assessed using questionnaires and surveys. Data was analyzed using logistic regression to determine the association of depression with allergic disease while controlling for age, sex, body mass index, smoking experience, and alcohol use. RESULTS: Asthma and atopic dermatitis were associated with a higher prevalence of depression (17.2% and 13%, respectively). After adjusting for the covariates, asthma patients were approximately two times as likely to have depression as non-allergic participants (odds ratio, 1.81; 95% confidence interval, 1.22-2.68). Psychosocial stress significantly increased in the following order: no allergy, any allergy without asthma, asthma only, and asthma with any allergy (p for linear trend = 0.01). The asthma without other allergies group showed the highest prevalence of cigarette smoking (p = 0.007). CONCLUSIONS: In this study, asthma with or without other allergies was significantly related to increases in depression, psychosocial stress, and smoking experience. Thus, care should be taken to adjust treatment to account for the psychological symptoms and health risk behaviors common among asthmatic adolescents.

An investigation of symptoms predating CFS onset.

The Fukuda et al. (1994) criteria for chronic fatigue syndrome (CFS) specifies that a symptom can only be included within a diagnosis if it is experienced concurrently or following the onset of fatigue. In order to investigate this issue, participants provided information on persisting symptoms (lasting greater than six months) and whether those symptoms occurred prior to, concurrently, or following the onset of their fatigue. More symptoms were experienced after the fatigue onset than prior to the fatigue onset; however, a considerable number of participants reported experiencing persisting symptoms prior to the onset of CFS. Particularly, rates of hay fever and asthma were higher prior to the illness. Investigating symptoms prior to the onset of the illness might provide investigators with ways to better understand the etiology of this illness.

Nasal and bronchial response to exercise in children with seasonal allergic rhinitis out of the pollen season.

BACKGROUND: Allergic rhinitis is a type I allergic disease of the nasal mucosa, and is characterized by paroxysmal sneezing, watery rhinorrhea, and nasal blockage. In seasonal allergic rhinitis subjects, even subthreshold allergen doses have been found to cause inflammatory cell infiltration in the nasal mucosa. This study aimed to investigate the presence of nasal obstructions and symptoms in seasonal allergic rhinitis subjects by assessing an exercise challenge test (ECT) outside of the pollen season. METHODS: Twenty patients and 20 healthy children who were admitted to the Osmangazi University Medical School Pediatric Allergy Clinic were included in the study in a pollen free season. The total nasal airflow and visual analog scale (for rhinorrhea, nasal congestion, sneezing, and itching) and pulmonary function tests were evaluated before and after each ECT. The nasal airflow and resistance changes were evaluated with anterior rhinomanometry. RESULTS: Eight patients and one healthy child had nasal obstructions after the ECT. There was a significant difference in the exercise-induced nasal obstructions between the 2 groups (p = 0.02). Eighteen children with exposure to tobacco smoke in the patient and control groups had lower forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25% to 75% (FEF25-75 ) values than the children without exposure to tobacco smoke. CONCLUSION: The prevalence of exercise-induced nasal obstruction in children with seasonal rhinitis out of the pollen season is 40%. We showed that minimal persistent inflammation and nasal symptoms can also be diagnosed in rhinitis children in a symptom-free period.

Effects of pollen season on central and peripheral nitric oxide production in subjects with pollen asthma.

BACKGROUND: Pollen exposure of allergic subjects with asthma causes increased nitric oxide (NO) in exhaled air (FENO) suggestive of increased airway inflammation. It is, however, unclear to what extent NO production in peripheral airways and alveoli are involved. OBJECTIVES: The aim of the present investigation was to analyze the relationship between central and peripheral components of FENO to clarify the distribution of pollen induced inflammation in asthma. SUBJECTS AND METHODS: 13 pollen allergic non-smoking subjects with mild-intermittent asthma and 12 healthy non-smoking control subjects were examined with spirometry and FENO at flows between 50 and 270 mL/s during and out of pollen season. RESULTS: Spirometry was normal and unaffected by season in subjects with asthma as well as controls. Out of season subjects with asthma had significantly higher FENO, elevated airway production (JáwNO) and preacinar/acinar production (CANO) than controls. Pollen exposure resulted in significantly increased FENO and JáwNO but not CANO. FENO among controls were not affected by season. Individual results showed, however, that CANO increased substantially in a few subjects with asthma. The increased CANO in subjects with asthma may be explained by increased NO production in preacinar/acinar airways and back diffusion towards the alveoli. CONCLUSIONS: The findings may indicate that subjects with allergic asthma have airway inflammation without alveolar involvement outside the pollen season and pollen exposure causes a further increase of airway inflammation and in a few subjects obstruction of intra acinar airways causing impeded back diffusion. Increased NO production in central airways, unassociated with airway obstruction could be an alternative explanation. These effects were not disclosed by spirometry.

Therapeutic evaluation of outpatient submucosal inferior turbinate surgery for patients with severe allergic rhinitis.

BACKGROUND: Surgical treatment for inferior turbinate (IT) is selected to treat severe allergic rhinitis (AR) that is unresponsive to conservative treatment. This study aimed to determine the clinical effects of outpatient submucosal IT surgery (OSITS) on patients with severe AR. METHODS: Between January 2008 and August 2012, 95 patients with severe AR who underwent OSITS at the Department of Otolaryngology, Hyogo College of Medicine, were retrospectively analyzed. There were 53 men and 42 women. Their mean age was 27 years (11-75 years). OSITS was bilaterally performed using a bipolar radiofrequency electrocautery under local anesthesia. Symptoms, QOL, and physical findings were evaluated using scores from both pre- and postoperative periods (average: 12.4 months), according to Practical Guideline for the Management of AR in Japan 2009. RESULTS: In perennial AR, all mean scores of nasal symptoms, QOL, and physical findings significantly improved after OSITS (p < 0.05, n = 83). Nasal obstruction, sleep problems, and IT congestion were the most strongly affected. Eye symptoms were not influenced by OSITS. OSITS also showed significant effects on nasal obstruction and IT congestion in seasonal AR (p < 0.05, n = 12), but not sneezing, nasal discharge, and QOL. In terms of the efficacy, OSITS was beneficial in 90% of perennial AR cases and 75% of seasonal AR cases. Epistaxis (1%), vestibulitis (1%), and IT atrophy (4%) were observed after OSITS. CONCLUSIONS: These data indicate that OSITS using radiofrequency electrocautery could be a beneficial therapeutic option in patients with severe AR.

Increased cys-leukotrienes in exhaled breath condensate and decrease of PNIF after intranasal allergen challenge support the recognition of allergic rhinitis in children.

Exhaled breath condensate (EBC) contains various mediators of inflammation. Since their concentrations correlate with severity of inflammatory response, EBC assessment allows non-invasive detection of various respiratory tract diseases and enables monitoring of their progression or treatment effectiveness. In this study, authors evaluate the usefulness of cysteinyl leukotrienes (cysLT) measurement in EBC, as non-invasive diagnostic markers of allergic rhinitis in children. It has been found that the assessment of cysLT in EBC, when performed out of the natural allergen exposure, can discriminate between healthy and allergic rhinitis individuals, with sensitivity 87.8% and specificity 76.4%, at the threshold level 39.05 pg/ml. The change of peak nasal inspiratory flow (ΔPNIF), measured before and after intranasal allergen challenge allowed recognition of healthy/allergic rhinitis-suffering individuals with sensitivity 76.8% and specificity 78.6%, at the threshold level of -3.2 l/min. When ΔPNIF assessment was combined with the measurement of cysLT in EBC, the sensitivity of such diagnostic approach reached 100% and its specificity increased up to 84.6%. The proposed algorithm was found to sufficiently discriminate between allergic rhinitis-suffering and healthy children, however, its clinical usefulness especially in young children requires further studies.

La rinitis alérgica local es una entidad prevalente inducida por alérgenos inhalados estacionales y perennes / Local allergic rhinitis is a prevalent entity induced by seasonal and perennial inhalant allergens

La rinitis alérgica local (RAL) es un nuevo fenotipo de rinitis con producción nasal de anticuerpos IgE específicos en ausencia de atopia sistémica que puede afectar a sujetos previamente diagnosticados de rinitis no alérgica y rinitis idiopática. Esta nueva entidad se caracteriza por la existencia de síntomas clínicos sugestivos de rinitis alérgica, producción local de IgE específica y presencia de un patrón inflamatorio Th2 en la mucosa nasal durante la exposición natural, así como tras la prueba de provocación nasal con alérgenos con producción local de IgE específica, triptasa y proteína catiónica de eosinófilos (ECP). La existencia de esta nueva entidad hace necesaria la realización de un diagnóstico alergológico preciso en pacientes con síntomas sugestivos de rinitis alérgicas cuando el prick test y la determinación de IgE específica sérica sean negativos. La detección local de anticuerpos IgE específicos en las secreciones nasales durante la exposición natural a aeroalérgenos y la respuesta positiva a la prueba de provocación nasal con aeroalérgenos con producción local de triptasa, ECP e IgE específica han demostrado ser una aproximación adecuada para detectar pacientes con RAL.

Allergic rhinitis and vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) was identified in 1980s as a protein that increases vascular permeability and induces endothelial cell-specific mitosis. VEGF plays an important role in angiogenesis during the embryonic stage and in angiogenesis and in increasing vascular permeability during postnatal life, both physiologically and pathologically. Great progress has been made in studies of VEGF, mainly in the field of oncology, and VEGF-targeted therapy has been successfully used to treat patients with cancer. In research related to chronic inflammation, several reports concerning rheumatoid arthritis or retinopathy and VEGF have been published. In the lower respiratory tract, increased levels of VEGF have been detected in biological samples from patients with asthma. However, VEGF has not been studied in detail in upper-airway diseases, such as rhinosinusitis. This review article focuses on VEGF and allergic rhinitis to advance studies of VEGF in chronic inflammation of the upper respiratory tract. VEGF levels in nasal secretions and nasal lavage fluid were higher in perennial allergic rhinitis than in nonallergic rhinosinusitis, after, rather than before, the antigen provocation test. The major VEGF isoforms were confirmed to be VEGF121 and VEGF165 in allergic rhinitis. Expression of VEGF mRNA was higher in serous versus mucous acini. In allergic rhinitis, serous acini produced significant quantities of VEGF, which was hypersecreted after antigen provocation. VEGF seems to play an important role in the pathophysiology of allergic rhinitis. Modulation of VEGF function seems to contribute to the successful treatment of conditions with airway inflammation such as allergic rhinitis.

Climate change and its impact on allergic rhinitis and other allergic respiratory diseases.

PURPOSE OF REVIEW: To discuss current evidence of global climate change and its implications for allergic rhinitis and other allergic respiratory diseases. RECENT FINDINGS: Global climate change is evidenced by increasing average earth temperature, increasing anthropogenic greenhouse gas levels, and elevated pollen levels. Pollutants of interest include carbon dioxide (CO2), ozone (O3), and nitrous oxide (NO2) because they can enhance the allergic response and lead to increased symptoms of allergic respiratory diseases. Heightened CO2 levels stimulate pollen production via photosynthesis and increased growth in multiple plant species investigated. Although worsened air quality appears to increase prevalence of allergic rhinitis, the effects of increased temperature are less certain. The findings of increased aeroallergen levels likely contribute to increases in presentation of allergic diseases, although more healthcare impact studies are necessary. SUMMARY: Although recent literature indicates and strongly supports changes in temperature, pollution levels, and aeroallergen levels, more longitudinal epidemiologic surveillance of allergic diseases in relation to climate change as well as pathophysiologic studies on changing aeroallergen effects on allergic diseases are needed.

Comparison of orally exhaled nitric oxide in allergic versus nonallergic rhinitis.

BACKGROUND: Fractional exhaled nitric oxide (FeNO), a well-known marker of airway inflammation, is rarely evaluated in rhinitis of different etiology. We aimed to compare the eNO levels in allergic rhinitis (AR) and nonallergic rhinitis (NAR) with/without asthma, as well as the contributing factors that interfere with elevated FeNO. METHODS: Patients were enrolled based on chronic nasal symptoms. Orally exhaled NO was measured with the single exhalation method at 50 mL/s. All subjects underwent a panel of tests: skin-prick tests, asthma control test, blood sampling, spirometry, and health-related quality-of-life questionnaires. RESULTS: The study group consisted of mainly women (130 women/41 men), with a mean age of 32.6 ± 13.2 years. AR was diagnosed in 122 (78.2%), NAR in 34 (21.8%), and 15 subjects were healthy controls. FeNO was insignificantly higher in patients with AR compared with patients with NAR and controls (32.2 parts per billion [ppb] versus 27 and 19.4 ppb), with no difference between genders. NAR + asthma had higher FeNO than those without asthma (40.5 ppb versus 14.9 ppb; p < 0.03), whereas accompanying asthma did not affect FeNO levels in the AR group. AR ± asthma had significantly higher FeNO levels than the NAR-only group (p < 0.01). Among AR + asthma, perennial sensitization caused higher FeNO levels than did seasonal allergens (48.5 ± 33.9 and 19.5 ± 13.6' p = 0.003), whereas FeNO was significantly higher during the allergen season. Nasally inhaled corticosteroids insignificantly reduced FeNO levels in all groups. Severity and seasonality of rhinitis, asthma, and ocular symptoms, but not gender, age, body mass index, Total IgE, forced expiratory volume in 1 second, and smoking, were associated with FeNO. CONCLUSION: Rhinitis and comorbid asthma are responsible for increased FeNO, irrespective of atopy. However, NAR without asthma may not be considered as a strong risk factor for airway inflammation.

Pilot evaluation of the nasal nitric oxide response to humming as an index of osteomeatal patency.

BACKGROUND: Paranasal sinuses are reservoirs for nitric oxide (NO), and humming facilitates nasal diffusion of NO. The nasal NO response to humming has previously been shown to be blunted with chronic sinusitis and nasal polyposis. We hypothesized that the nasal NO response to humming will be proportional to radiographic osteomeatal patency when comparing allergic rhinitis (AR) patients (without chronic sinusitis) with normal controls. METHODS: Nonsmoking subjects completed questionnaires and skin-prick testing. Subjects underwent sinus CT scanning, followed by exhaled (oral) and nasal NO sampling (with and without humming). Humming-to-quiet (H/Q) nasal NO ratios were calculated. Three-dimensional reconstructions were used to trace the osteomeatal complex (OMC) and measure minimum cross-sectional area. Lund-Mackay scores were also documented. RESULTS: A total of 33 subjects (22 women; mean age, 35.5 years) completed the study. Seventeen AR patients (5 IAR and 12 PAR) participated, as did 16 nonallergic controls. Among controls, quiet nasal NO levels--corrected for fractional exhaled NO--rose significantly with OMC area and fell significantly with Lund-Mackay scores (p < 0.05). However, we observed no proportionality between H/Q ratio and radiographic OMC patency. CONCLUSION: Analysis of nasal NO samples taken under quiet conditions from normal controls was consistent with the paranasal sinuses acting as a reservoir of nasal NO and with OMC patency acting as a significant factor in NO diffusion. However, our results did not support a relationship between the nasal NO response to humming and radiographic OMC patency in a sample excluding subjects with severe rhinosinusitis.