Nasal Nasal Nitric Oxide Research Articles

Predictive Value of Nasal Nitric Oxide for Diagnosing Eosinophilic Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis.

The primary aim of this study was to assess disparities in nasal nitric oxide (NO) levels between individuals diagnosed with eosinophilic chronic rhinosinusitis (ECRS) and those without ECRS. The second aim was to ascertain the comparative predictive efficacy of these nasal NO levels for the presence of ECRS. A systematic analysis was conducted on relevant studies that compared nasal NO levels in individuals with ECRS and those without. Furthermore, the discriminatory capacity of nasal NO in distinguishing ECRS from non-ECRS cohorts was quantified. The risk of bias across studies was evaluated utilizing the Newcastle-Ottawa scale. The comprehensive review encompassed a total of 5 studies involving 470 participants. Findings revealed that patients diagnosed with ECRS exhibited significantly higher levels of nasal NO, as measured in parts per billion (ppb), compared to their non-ECRS patients. The mean difference was 130.03 ppb (95% confidence interval: [66.30, 193.75], I2 = 58.7%). The diagnostic odds ratio for nasal NO in identifying ECRS was 9.29 ([5.85, 14.75], I2 = 26.4%). The area under the summary receiver operating characteristic curve was 0.82. The correlation between sensitivity and false positive rate was 0.53, suggesting a lack of heterogeneity. Sensitivity, specificity, negative predictive value, and positive predictive value were 69% ([0.55, 0.79], I2 = 77.0%), 83% ([0.73, 0.90], I2 = 68.5%), 77% ([0.69, 0.83], I2 = 50.1%), and 75% ([0.67, 0.82], I2 = 41.5%), respectively. Nasal NO has the potential as a noninvasive diagnostic measure and endotype tool for ECRS.

Measurements of upper and lower airway nitric oxide in healthy adults

Introduction. Nasal nitric oxide (NO) measurement can be a useful tool for monitoring upper airway diseases. However, there is a considerable lack of validation data. Aims. To evaluate the repeatability and intra-subject variations of nasal NO output (nV NO) in healthy adults and to study its correlation with lower airway NO parameters. Methods. nV NO was measured in healthy non-smokers at baseline (N = 31, age: 28 ± 6 years), after 1 h (N = 15), 1 d (N = 15), 1 week (N = 17), and compared using the Bland–Altman method. At baseline, lower airway NO parameters (F ENO, flux of NO in the conducting airways and alveolar NO concentration) were also measured and correlated to nV NO (Spearman correlation). Multivariate regression analysis was used to assess the factors influencing nV NO. Results. Baseline median nV NO was 465 (interquartile range (IQR) = 404–536) nL min−1. The mean differences between the baseline and repeated measurements were not significant (p > 0.05). The coefficient of repeatability (mean: 118, IQR = 88–181 nL min−1) and coefficient of variation (mean: 9.1%) were low. We found no correlation between nV NO and lower airway NO parameters (p > 0.05). Sex (β = −0.52, p = 0.02) and body weight (β = −0.65, p = 0.03) influenced nV NO (model: p = 0.04, R 2 = 0.31). Conclusion. nasal NO output has good repeatability in healthy adults. The NO productions of lower and upper airways are not related in health, but nasal NO output seems to be affected by sex and body weight.

Novel compound heterozygous mutations of DNAH5 identified in a pediatric patient with Kartagener syndrome: case report and literature review

BackgroundKartagener syndrome is a subtype of primary ciliary dyskinesia that may exhibit various symptoms including neonatal respiratory distress and frequent infections of the lung, sinus and middle ear because of the impaired function of motile cilia. In addition to typical symptoms of primary ciliary dyskinesia, patients with Kartagener syndrome also show situs inversus. It is an autosomal recessive disorder which is mostly caused by mutations in DNAH5. Kartagener syndrome is often underdiagnosed due to challenges in the diagnosis process. As next-generation sequencing becomes widely used in clinical laboratories, genetic testing provides an accurate approach to the diagnosis of Kartagener syndrome.Case presentationA 7-year-old female patient presented with runny nose of 6 years duration and recurrent cough with phlegm of 2 years duration. Kartagener syndrome was diagnosed through diagnostic tests such as nasal nitric oxide (NO) concentration and transmission electron microscopy, and after performing other exams that corroborated the diagnosis, such as computed tomography, bronchoscopy and hearing test. Whole-exome sequencing was performed for the patient and both parents. The pediatric patient was diagnosed as Kartagener syndrome with the typical symptoms of ciliary dyskinesia including bronchiectasis, sinusitis, conductive hearing loss and situs inversus along with a reduced nasal NO concentration and ciliary abnormalities. The patient carried two novel compound heterozygous mutations in DNAH5, NM_001369:c.12813G > A (p. Trp4271Term) and NM_001369:c.9365delT (p. Leu3122Term). Both mutations lead to premature stop codons and thus are pathogenic. The p. Trp4271Term and p. Leu3122Term mutations were inherited from the father and the mother of the patient individually. A literature review was also conducted to summarize DNAH5 mutations in pediatric patients with Kartagener syndrome across different ethnic groups.ConclusionsOur study provides a good example of the diagnosis of Kartagener syndrome in pediatric patients using a series of diagnostic tests combined with genetic testing. Two novel loss-of-function mutations in DNAH5 were identified and validated in a pediatric patient with Kartagener syndrome.

Phenotypic features of ciliary dyskinesia among patients with congenital cardiovascular malformations.

Cilia are cell membrane-bound organelles responsible for airway mucus clearance, establishment of left-right organ asymmetry, cardiogenesis, and many other functions in utero. Phenotypic features suggestive of respiratory ciliary dyskinesia among patients with heterotaxy syndrome, defined as complex cardiovascular malformations (CVM) and situs ambiguus (SA), has not been adequately explored. We hypothesized that there is a greater incidence of phenotypic features consistent with ciliary dyskinesia among patients with heterotaxy syndrome compared to patients with other CVM and laterality defects without heterotaxy syndrome. Thirty six subjects were identified by medical record search and divided into four groups based on situs status and type of CVM as follows: SA and complex CVM (group 1); SA and simple CVM (group 2); situs solitus and complex CVM (group 3); and situs solitus and simple CVM (group 4). Phenotype was assessed with a clinical questionnaire, nasal nitric oxide (NO) level, and pulmonary function testing. Those with complex CVM underwent additional testing for variants in genes involved in ciliary structure and function. The mean nasal NO level was significantly lower among all subjects with complex CVM regardless of situs anomalies (groups 1 and 3). There was no significant difference in respiratory symptoms or lung function among the four groups. No bi-allelic genetic mutations were detected among patients with complex CVM. This study identified a relatively lower mean nasal NO level, suggestive of relative ciliary dyskinesia, among subjects with complex CVM. Pulmonary function and clinical symptoms did not reflect significant pulmonary disease among those with complex CVM.

Nasal nitric oxide in the inferior turbinate surface decreases with intranasal steroids in allergic rhinitis: A prospective study

ObjectiveIt remains controversial whether nasal nitric oxide (NO) serves as a reliable parameter to evaluate treatment efficacy in patients with allergic rhinitis (AR). The measurement of local nasal NO levels has been shown to be a sensitive marker for the diagnosis of symptomatic AR patients. Here we assessed the applicability of nasal NO to evaluations of the efficacy of intranasal steroids (INS) in a prospective design. MethodsWe enrolled 25 patients with perennial AR and 10 age-matched healthy participants. The AR patients received fluticasone furoate (FF) once daily for 2 months. Fractional exhaled NO and nasal NO measurements were carried out using an electrochemical analyzer at pretreatment and at 2 weeks and 2 months after treatment. Nasal NO levels were directly measured at two different areas of the nasal cavity: the surface of the inferior turbinate (IT area) and the front of the middle meatus (MM area). Subjective nasal symptoms were also recorded at each visit. ResultsThe mean total nasal symptom score in the AR patients decreased significantly after FF treatment (p<0.0001). The mean nasal NO levels in the IT area in the AR patients were significantly higher at pretreatment than those of the healthy participants (109 vs. 62.5 ppb, respectively; p<0.001). After FF administration, the nasal NO levels in the IT area of the AR group showed a significant reduction at both 2 weeks and 2 months (79.1 and 71.9 ppb, respectively; p<0.05 and p<0.01). There was no significant difference in nasal NO levels in the MM area between the controls and the AR group at any visit timepoint. When the ratio of the MM area to the IT area (MM/IT ratio) was plotted for each subject, the untreated AR patients showed a marked decrease in the ratio, whereas after the FF treatment, the AR patients' mean MM/IT ratios showed a significant increase. No significant difference compared to the control group existed at 2 months. ConclusionNasal NO measurement around the inferior turbinate is an objective measure to evaluate allergic conditions and is useful to monitor therapeutic effects of INS.

Infant nasal nitric oxide over time: natural evolution and impact of respiratory tract infection.

Nasal nitric oxide (NO) discriminates between patients with primary ciliary dyskinesia (PCD) and healthy individuals. We report feasibility of measurement and natural evolution of nasal NO and upon the impact of respiratory tract infection (RTI) on nasal NO in healthy infants (HI), followed from birth until age 2 years, with comparison to nasal NO in infant PCD.Tidal-breathing nasal NO measurements were performed at scheduled visits at 2 weeks old and at 4, 8, 12, 18 and 24 months old, with extra visits during RTIs. Historical nasal NO measurements for infant PCD were included for comparison.Altogether, 224 nasal NO measurements were performed in 44 enrolled infants. Median newborn nasal NO was 46 ppb (interquartile range (IQR) 29-69 ppb), increasing at a rate of 5.4% per month up to 283 ppb (IQR 203-389 ppb) at the age of 2 years. RTIs in 27 out of 44 infants temporarily suppressed nasal NO by 79%. Values for nasal NO in seven infants with PCD ranged from 6-80 ppb. The success rate to accept nasal NO sampling was 223 out of 224 measurements (99.6%).Tidal-breathing nasal NO measurement was indeed feasible in infancy and nasal NO in HI increased significantly up to 2 years of age, in opposition to nasal NO in PCD cases, which stayed low past 2 years of age. RTI episodes caused marked, temporary reductions in nasal NO in HI indistinguishable from that in infant PCD, suggesting that nasal NO should be measured in RTI-free intervals.

Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder associated with lower airway disease. However, only few studies of CRSwNP from outside secondary/tertiary care centres have been published. We recently reported an asthma frequency of 44% and 65% in primary and secondary care patients respectively. Therefore, we hypothesise that inflammation of the lower airways could be present in all CRSwNP patients, even without asthma. Here, we assessed the degree of lower and upper airway inflammation using exhaled and nasal nitric oxide (NO) in primary care CRSwNP patients with and without asthma. Fifty-seven patients who met the EPOS criteria for CRSwNP were prospectively recruited from primary care ear, nose and throat clinics. Nasal endoscopy was performed by an ear, nose and throat specialist upon enrolment. Additionally, 30 healthy controls were enrolled. Expiratory and nasal NO measurements and thorough pulmonary evaluation were performed. Pulmonary disease was diagnosed by a respiratory physician. Fifty-nine percent of CRSwNP patients with asthma showed elevated expiratory NO; the same was seen in 29% of non-asthmatic CRSwNP patients. Compared with controls, a high level of exhaled NO was significantly more prevalent in CRSwNP irrespective of asthma-status. Nasal NO was significantly lower in patients with CRSwNP compared with controls. Subclinical eosinophilic lower airway inflammation is common in CRSwNP in the primary sector, even in the absence of asthma.

Nasal ventilation is an important factor in evaluating the diagnostic value of nasal nitric oxide in allergic rhinitis.

The role of nasal nitric oxide (NO) in the diagnosis of allergic rhinitis (AR) is controversial. The aim of this study was to identify factors that may affect levels of nasal NO in AR patients and evaluate the role of nasal NO in the diagnosis of AR. Seventy-five AR patients and 31 healthy controls were enrolled in this study. AR symptom scores were assessed using the visual analog scale. Eosinophil cationic protein (ECP) was detected by enzyme-linked immunoassay, nasal NO was measured using a chemiluminescence analyzer, and nasal airway resistance (NAR) was assessed by active anterior rhinomanometry. Nasal obstruction score, ECP, and NAR were found to be independently associated with nasal NO. Nasal NO level in patients with nasal obstruction score<7 (mild-to-moderate obstruction) was significantly increased compared with healthy subjects (282.1±122.6 vs 150.7± 48.4 ppb; p<0.001), and significantly decreased in patients with nasal obstruction score≥7 (severe obstruction) (97.2±52.2 vs 150.7±48.4 ppb; p<0.001). Nasal NO and ECP in secretion were positively correlated in patients with mild-to-moderate nasal obstruction (r=0.678), but not in patients with severe nasal obstruction (r=0.077). In patients with NAR <0.65 Pa/cm3 /s, the correlation coefficient was highest between NO and ECP (r=0.685). The areas under the receiver operating characteristic curve for nasal NO level were 0.878 and 0.939 in patients with nasal obstruction scores<7 and NAR<0.65Pa/cm3 /s, respectively. Nasal patency affects nasal NO level significantly, and may reflect the severity of nasal inflammation in AR patients with mild-to-moderate nasal obstruction, but not in patients with severe nasal obstruction.

Xylitol nasal irrigation in the treatment of chronic rhinosinusitis

ObjectiveTo evaluate the efficacy of xylitol nasal irrigation (XNI) treatment on chronic rhinosinusitis (CRS) and to investigate the effect of XNI on nasal nitric oxide (NO) and inducible nitric oxide synthase (iNOS) mRNA in maxillary sinus. Materials and methodsPatients with CRS were enrolled and symptoms were assessed by Visual Analog Scale (VAS) and Sino-Nasal Outcome Test 22 (SNOT-22). Nasal NO and iNOS mRNA in the right maxillary sinus were also examined. Then, they were treated with XNI (XNI group) or saline nasal irrigation (SNI, SNI group) for 30days, after which their symptoms were reassessed using VAS and SNOT-22, and nasal NO and iNOS mRNA in the right maxillary sinus were also reexamined. ResultsTwenty-five out of 30 patients completed this study. The scores of VAS and SNOT-22 were all reduced significantly after XNI treatment, but not after SNI. The concentrations of nasal NO and iNOS mRNA in the right maxillary sinus were increased significantly in XNI group. However, significant changes were not found after SNI treatment. Furthermore, there were statistical differences in the assessments of VAS and SNOT-22 and the contents of nasal NO and iNOS mRNA in the right maxillary sinus between two groups. ConclusionsXNI results in greater improvement of symptoms of CRS and greater enhancement of nasal NO and iNOS mRNA in maxillary sinus as compared to SNI.

Clinical characteristics of primary ciliary dyskinesia

To analyze the clinical characteristics of primary ciliary dyskinesia(PCD) so as to improve the diagnostic level of this rarely seen disease. Ten patients with PCD were retrospectively reviewed, the medical history, symptoms, signs, lung CT or chest X-ray, rhino-sinus CT scan, nasal nitric oxide (NO) levels, nasal ciliary ultrastructure, DNAH5 and DNAH11 genetic mutation, as well as treatment outcome were analyzed. All 10 patients had recurrent chronic sinusitis, otitis media, bronchitis/bronchiectasis since childhood. Nine cases with translocation of heart and big vessels were diagnosed as Kartagener syndrome. One woman was suffering from barrenness and one man sterility after marriage for long time without birth control. Nasal NO levels were significantly lower in 2 patients with PCD but it was almost normal in one patient. Ciliary ultrastructure investigated by transmission electron microscope were almost normal in 4 cases without missing of inner or outer dynein arms. Two cases taking exome capture sequencing showed that mutations happened in DNAH5 and DNAH11. Five subjects underwenting sanger sequencing on 6 common exon fragments of DNAH5 and DNAH11 did not show any abnormality. Ten cases took medication therapy, while 5 patients once underwent functional endoscope sinus surgery. All of the 10 patients had improvement of their symptoms and signs after treatment. The PCD is so rare in clinic that it is easily misdiagnosed. Clinical characteristics, nasal NO levels, ciliary ultrastructure and genetic testing are significant for clinical diagnosis.

Comparison of Nasal Nitric Oxide Levels between the Inferior Turbinate Surface the Middle Meatus in Patients with Symptomatic Allergic Rhinitis

Because of the anatomical complexity and the high output of the human nose, it has been unclear whether nasal nitric oxide (NO) serves as a reliable marker of allergic rhinitis (AR). We examined whether nasal NO levels in the inferior turbinate (IT) surface and the middle meatus (MM) differ in symptomatic AR patients. We measured fractional exhaled NO (FeNO) and nasal NO in normal subjects (n = 50) and AR patients with mild symptoms (n = 16) or moderate or severe symptoms (n = 27). Nasal NO measurements were obtained using an electrochemical analyzer connected to a catheter and an air-suction pump (flow rate 50mL/sec). Compared to the normal subjects, the AR patients showed significantly higher nasal FeNO and nasal NO levels in the IT area. No significant difference in the MM area was observed among the three groups. The MM area showed higher NO levels than the IT area in all three groups. The ratio of nasal NO levels of the MM area to the IT area (MM/IT ratio) was significantly lower in the AR groups. The moderate/severe AR patients showed significantly higher nasal NO in the IT area (104.4 vs. 66.2ppb) and lower MM/IT ratios than those in the mild AR patients. The analysis of nasal brushing cells revealed significantly higher eosinophil cationic protein and nitrotyrosine levels in the AR groups. Nasal NO assessment in the IT area directly reflects persistent eosinophilic inflammation and may be a valid marker to estimate the severity of AR.

Nasal and Exhaled Nitric Oxide in Chronic Rhinosinusitis with Polyps

The ciliary epithelial cells in the paranasal sinuses produce nasal nitric oxide (NO) continuously and plays a variety of roles in the paranasal sinuses. The purpose of this study was to assess whether we can use the levels of nasal NO (nNO) and exhaled NO (eNO) as a tool for evaluation in chronic rhinosinusitis (CRS) with nasal polyp patients. We used chemiluminescent NO analyzer to measure nNO and eNO among normal controls (32) and CRS with polyp (30) and CRS with polyp and allergic rhinitis patients (27) and compared it with various clinical symptoms, laboratory data, and computed tomography (CT) scores. Levels of nNO were significantly lower in patients with CRS with polyps (88.5 ± 54.7 ppb) compared with controls (241.0 ± 89.5 ppb). Levels of nNO in CRS with polyps and allergic rhinitis (167.0 ± 47.6 ppb) were significantly higher than CRS with polyps and lower than controls. A significant inverse relationship was observed between nNO and sinus CT scores, severity of nasal obstruction, and purulent rhinorrhea in CRS with polyps. Low values of nNO separated well patients with CRS with polyps, and the cutoff value of <163 ppb was associated with the best combination of specificity (93%) and sensitivity (81%). A significant positive relationship was observed between eNO and CT scores. The nNO could be used for another screening of CRS with polyps for the more severe phenotypes, which may eventually have to be treated with surgery.

原発性線毛運動不全症―最近の進歩

Primary ciliary dyskinesia (PCD) is a hereditary disorder with structural and/or functional impairment of the cilia of the whole body. PCD is characterized by chronic sinusitis, bronchiectasis, male infertility and ectopic pregnancy due to impaired ciliary motility. The prevalence of PCD is estimated at 1 in 20,000 live births. Cases with situs inversus are termed “Kartagener’s syndrome” and usually these diagnoses are not difficult to make. However, in cases without situs inversus, the diagnosis can be very difficult. As such, it is most likely that PCD without situs inversus is underdiagnosed at the present time. The diagnosis of PCD is made when the patients have characteristic clinical features and (1) structural abnormalities of the cilia observed with electron microscopy and/or (2) presence of mutations in one of the genes associated with PCD. Electron microscopic diagnosis is not easy because ultrastructural ciliary defects can also be found in a few cilia among the healthy populations. Measuring levels of nasal nitric oxide (NO) concentration is a very useful tool in screening for PCD, because low NO values are a feature of PCD. Hand-held devices using tidal breathing are as useful as stationary devices. The sensitivity and specificity of nasal NO levels of <250 ppb for diagnosing PCD were 97% and 90%, respectively. Some other features can help to diagnose PCD. Frontal sinuses and sphenoid sinuses are hypoplastic. Having a combination of rhinosinusitis, middle ear and lung diseases increases the probability of PCD. The effectiveness of endonasal sinus surgery to treat rhinosinusitis associated with PCD is controversial.

Thirty Minute-Exposure to Aged Cigarette Smoke Increases Nasal Congestion in Nonsmokers

The aim of this study was to assess the effects of short exposures to experimentally aged cigarette smoke on the nose and upper airways. This crossover study compared the effects of 30-min exposures to (1) experimentally aged cigarette smoke at 1 mg/m3 particulate matter (PM)/14 ppm carbon monoxide (CO) and (2) conditioned filtered air on urinary metabolites of nicotine and tobacco-specific nitrosamines. Subjective nasal symptoms were assessed by questionnaire, objective nasal congestion was assessed by anterior rhinomanometry and nasal nitric oxide (NO) concentrations were determined. Experimentally aged cigarette smoke is a validated model for secondhand smoke (SHS). Twenty-six healthy nonsmokers (10 normal, 7 atopic/nonrhinitic, 7 atopic rhinitic, 2 nonatopic/rhinitic) were studied. A 30-min exposure to SHS increased nasal resistance in healthy nonsmokers. The rise in nasal resistance was most pronounced in rhinitic subjects. Significant increases were not noted when atopic subjects were considered independent of rhinitis status. Secondhand smoke exposure also elevated subjective nasal symptoms and urinary concentrations of metabolites of nicotine (cotinine and trans-3´-hydroxycotinine) and tobacco-specific nitrosamines [(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)] in all subgroups of subjects. Exposure-related, subjective nasal symptoms were significantly higher in rhinitic than in normal subjects. Significant changes in nasal NO concentrations were not detected. Data indicate a 30-min exposure to secondhand smoke at 1 mg/m3 PM increases subjective upper respiratory symptoms, increases urinary cotinine and NNAL, and produces objective nasal airflow obstruction in human subjects.

Nasal nitric oxide levels do not allow for discrimination between olfactory loss due to various etiologies

Nasal nitric oxide (NO) and olfactory function are decreased in patients with chronic inflammatory sinonasal disease, suggesting a link between these two parameters. The aim of the study was to investigate nasal NO levels in patients with olfactory dysfunction due to different causes. Prospective study in a university clinic setting (tertiary referral center). Posttraumatic (n = 11), idiopathic (n = 13), and sinonasal-related olfactory-impaired patients (n = 55) were compared with healthy subjects (n = 11). Nasal NO levels, olfactory testing (Sniffin' Sticks), and rhinosinusitis questionnaires (Short-Form 36, Sinonasal Outcome Test 22, Rhinosinusitis Disability Index) were obtained. No significant difference in nasal NO levels were found between the different olfactory dysfunction causes. Nasal NO correlated negatively with age and positively with overall olfactory function, olfactory discrimination, and identification but not with olfactory thresholds. The more nasal symptoms prevailed in the Rhinosinusitis Disability Index, the lower the nasal NO. Nasal NO levels do not allow for discrimination between olfactory loss due to various etiologies based on the present data. Nasal NO production seems to decrease with age and also seems to be associated to overall olfactory function and in particular to central nervous system tasks such as olfactory discrimination and identification but not to olfactory thresholds. These findings raise questions about the link and interaction between olfactory function and nasal NO.

Nasal nitric oxide in a random sample of adults and its relationship to sensitization, cat allergen, rhinitis, and ambient nitric oxide

There is conflicting evidence whether nasal nitric oxide (NO) is associated with current rhinitis and with other possible predictors. Most studies have been performed in clinical cohorts and there is a lack of studies based on a general population sample. The aim of the present study was to investigate predictors for levels of nasal nitric oxide (NO) in a general population. The population consisted of 357 subjects from Gothenburg participating in the follow-up of the European Respiratory Health Survey in 1999-2001. All subjects completed an extensive respiratory questionnaire. Nasal NO was measured from one nostril at a time with a sampling rate of 50 mL/s for 16 seconds and the nasal NO concentration was determined as the mean value within the plateau phase. Mattress dust samples were collected for cats and mites in a subsample of subjects. Ambient and exhaled NO was also measured. The predictors for nasal NO were analyzed in multiple linear regression models. There was no relation between the levels of nasal NO and reporting current rhinitis. Nasal NO was significantly increased among those with high levels of IgE against cats and current smokers had significantly lower nasal NO. There was also a positive association between ambient NO and nasal NO. There were no significant associations between nasal NO and sex, age, or height, or between nasal NO and measured levels of cat antigen. In this general population sample we found no relation between current rhinitis and nasal NO levels. There was a clear association between sensitization to cat and nasal NO, but there was no relation to current exposure to cat allergen. Our data support that nasal NO has a limited value in monitoring upper airway inflammation.

Efficacy of mometasone furoate nasal spray for nasal symptoms, quality of life, rhinitis-disturbed sleep, and nasal nitric oxide in patients with perennial allergic rhinitis

Intranasal corticosteroid therapy has exhibited effectiveness for improving nasal symptoms and quality of life (QOL) scores associated with seasonal allergic rhinitis. We prospectively investigated the efficacy of mometasone furoate nasal spray (MFNS) for improving the total nasal symptom score, QOL score, and sleep quality in subjects with perennial allergic rhinitis (PAR). Nasal airway conditions were also objectively assessed by measuring nasal nitric oxide (NO). Fifty-seven patients with PAR were randomized to MFNS or placebo for a 14-day, double-blind, crossover study. The subjects recorded their symptoms on nasal symptom forms and a visual analog scale. QOL and sleep quality were surveyed in accordance with the Japanese version of the Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) and the Japanese version of the Epworth Sleepiness Scale. Nasal NO was measured during a single exhalation using a chemiluminescence analyzer. MFNS treatment achieved significant reductions versus placebo for total nasal symptoms (p < 0.001). There were significant decreases of the usual daily activity domain (p < 0.005), outdoor activities (p < 0.01), social function (p < 0.05), and the overall QOL score (p < 0.05) of JRQLQ with MFNS therapy versus placebo. A significant reduction of the sleepiness scale was also observed in the MFNS group with high sleep disturbance (p < 0.01). A significant decrease of nasal NO was found in the MFNS group (p < 0.01), especially among patients with severe nasal symptoms (p < 0.005). This prospective study indicated that MFNS therapy significantly improves nasal symptoms, QOL, sleep quality, and upper airway condition in Japanese subjects with PAR.

The Challenges of Diagnosing Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic disorder of ciliary structure and function. The diagnosis can be challenging, particularly when using nongenetic assays. The "gold standard" diagnostic test is ultrastructural analysis of respiratory cilia obtained by nasal scrape or brush biopsy. A few specialized centers use high-speed videomicroscopy to examine ciliary beat. Certain beat patterns correlate with ultrastructural defects, and, in some cases, subtle alterations in beat pattern can be seen when ultrastructure is normal. Recent studies have shown that nasal nitric oxide (NO) is very low in patients with PCD compared with healthy control subjects; therefore, this assay may be a useful screening or adjunctive test for PCD. Because acute respiratory illnesses may yield alterations in ciliary ultrastructure, ciliary beat, and nasal NO values, these tests should be performed during a stable baseline period. Identification of an array of PCD genes has provided the opportunity for making a definitive genetic diagnosis for PCD in some cases. All of these approaches have a role in diagnosing PCD. For example, PCD has been confirmed by identifying disease-causing mutations in a heavy dynein chain gene in individuals with normal ciliary ultrastructure but subtle defects in ciliary beat and low nasal NO. Priorities to improve nongenetic diagnostic capability include standardization of nasal NO as a screening test and the development of specialized centers using uniform approaches for the analysis of ciliary ultrastructure and ciliary beat pattern. Another chapter in this issue (see Zariwala and colleagues, pp. 430) addresses the progress toward improved capabilities for definitive genetic testing.

Effect of systemic steroids on humming nasal nitric oxide in chronic rhinosinusitis with nasal polyposis

Increased nasal nitric oxide (NO) is a marker for paranasal sinus ostial patency. However, there are no data evaluating the effect of systemic steroids on humming nasal NO in chronic rhinosinusitis with nasal polyposis (CRSNP). To assess whether 2 weeks of oral steroids in CRSNP increases humming nasal NO, whether humming is a more sensitive indicator of this increase than other methods of measuring NO, and whether it correlates with improvements in clinical parameters for sinonasal disease. Adults with CRSNP (grade 2 and above) were treated with oral prednisolone, 25 mg/d for 2 weeks. Nasal NO was measured by aspiration, exhalation at 0.2 L·s⁻¹, and humming methods. Peak nasal inspiratory flow, Sinonasal Outcomes Test 20 score, symptoms, olfaction, and polyp grade were also measured before and after treatment. Twelve patients (mean age, 49 years) completed the treatment. The differences in nasal NO before and after steroid treatment were significantly less pronounced as measured by geometric mean-fold ratio with aspiration (1.5; 95% confidence interval [CI], 1.1 to 1.9; P = .009) and exhalation (2.1; 95% CI, 1.2 to 3.9; P = .02) compared with the humming technique (4.9; 95% CI, 2.2 to 10.7; P = .001). The standardized response means for the methods of NO estimation were 0.97 for aspiration, 1.05 for exhalation, and 1.61 for humming. This study demonstrates that humming nasal NO increases after 2 weeks of oral steroid therapy for CRSNP. Humming NO is more sensitive than aspiration and exhalation and is associated with improvements in symptoms, polyp size, and quality of life. Humming NO may fill the niche for a noninvasive marker of sinus ostial patency.

Diagnostic value of outcome measures following allergen exposure in an environmental challenge chamber compared with natural conditions

Efficacy testing of drugs in seasonal allergic rhinitis (SAR) is often disturbed by seasonal variations of environmental allergens, and assessment of onset and duration of action is hardly possible under natural conditions. Allergen provocation in an environmental challenge chamber (ECC) can be of added value in this respect. However, the specificity, sensitivity, and reproducibility of outcome measures under both settings are unclear. The aim of this study was to investigate and compare the diagnostic value (specificity, sensitivity, and reproducibility) of clinical end-points and biomarkers both following allergen provocation in an ECC and under natural conditions. Sixty adult patients with SAR to grass and 60 healthy subjects were exposed twice to grass pollen in an ECC and observed twice during the pollen season. Symptoms, nasal flow, as well as exhaled and nasal nitric oxide (NO) were investigated. The total nasal symptom score (TNSS) in the ECC had the best reproducibility (intraclass correlation coefficient ICC=0.86) and sensitivity/specificity [area under receiver operating characteristic curve (AUC)=0.99] of all measures. Symptoms in season also had good sensitivity/specificity but were far less reproducible. Nasal flow in the ECC had good sensitivity/specificity but reproducibility was limited. NO measurements showed good reproducibility but sensitivity/specificity were limited, except for exhaled NO in season (AUC=0.75). The high reproducibility and sensitivity/specificity in the ECC suggests that TNSS is a valuable outcome measure. While exhaled NO can be considered to monitor airway inflammation, nasal NO appears to be unspecific.