Exhaled and nasal NO measurement: NO in your breath doesn't imply a negative attitude!

Measurement of exhaled nitric oxide (NO) and nasal nitric oxide commenced in the 1990s shortly after the scientific world learned about the endogenous production of NO and its multiple roles in physiologic and pathologic processes. Exhaled NO is an established approved clinical test in asthma that can cast light on eosinophilic airway inflammation and the response to anti-inflammatory medications e.g.

Concordance for changes in allergic asthma domain variables after short-term corticosteroid therapy.

Background: Asthma is a complex syndrome with multiple domains including symptoms, lung function, asthma control, and airway inflammation. A study of Fenom PRO™, a novel monitor for exhaled nitric oxide (FeNO), provided an opportunity to look at concordance/discordance (C/D) for changes in multiple asthma domains over a 2-week period after corticosteroid therapy.

Methods: Non-steroid-treated adults and children with uncontrolled asthma had asthma domain measures, (FeNO), forced expired volume in 1 s (FEV), the 6-item Asthma Control Questionnaire scores (ACQ6), and daily asthma symptoms, assessed before and after a 2-week course of corticosteroids.

Patterns and determinants of exhaled nitric oxide trajectories in schoolchildren over a 7-year period.

Fractional exhaled nitric oxide ( ), a marker of allergic airway inflammation, is used in respiratory research and asthma clinical care; however, its trajectory with increasing age during childhood has not been well characterised. We examined longitudinally during a period of important somatic growth to describe trajectories across childhood and adolescence in healthy participants and evaluate clinical factors as potential determinants of trajectories. was collected at six visits over 8 years in a population-based cohort of 1791 schoolchildren without asthma (median age at entry 8.

Bruxism Relieved Under CPAP Treatment in a Patient With OSA Syndrome.

Bruxism is a heterogeneous condition related to various underlying mechanisms, including the presence of OSA. This case report illustrates that sleep mandibular movement monitoring and analysis could provide a useful opportunity for detection of both sleep bruxism and respiratory effort. The current case suggests that tracking of respiratory effort could enable evaluation of bruxism and its potential interactions.

Clinical precision, accuracy, number and durations of exhalations for a novel electrochemical monitor for exhaled nitric oxide.

Background: Exhaled nitric oxide (FeNO) is a validated marker of eosinophilic inflammation. Fenom Pro is a novel FDA-cleared monitor for FeNO. The American Thoracic Guidelines from 2005 recommend at least 6 s exhalation for adults and in some cases up to 10 s, and 4 s for children, and that the average of the first two valid exhalations is taken as the FeNO value.

Three Major Efforts to Phenotype Asthma: Severe Asthma Research Program, Asthma Disease Endotyping for Personalized Therapeutics, and Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome.

The SARP, ADEPT, and U-BIOPRED programs are all significant efforts in characterizing asthma and reporting clusters that will assist in designing personalized therapies for asthma, and especially severe asthma. Key aspects of the design of these programs are summarized and major findings are reported in this review.

Mandibular Movement Analysis to Assess Efficacy of Oral Appliance Therapy in OSA.

Rationale: The respiratory effort index derived from vertical mandibular movements (MM-REI) is a potential marker of increased respiratory effort during sleep. We evaluated the effectiveness of mandibular advancement splint therapy using MM-REI, in comparison with the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI).

Methods: Fifty-six subjects (median age, 47 years) with OSA treated with a custom mandibular advancement splint (Herbst appliance) were evaluated at the end of the titration procedure when snoring was reported absent by the sleep partner.

A phase 2a study of toreforant, a histamine H receptor antagonist, in eosinophilic asthma.

Background: Data from preclinical and clinical studies support the evaluation of histamine 4 receptor antagonists in the treatment of asthma. Toreforant is a selective histamine 4 receptor antagonist that could be effective in patients with eosinophilic asthma.

Objective: To evaluate the efficacy and safety of toreforant in patients with eosinophilic, persistent asthma that was inadequately controlled despite current treatment.

Inhaled Steroids and Active Smoking Drive Chronic Obstructive Pulmonary Disease Symptoms and Biomarkers to a Greater Degree Than Airflow Limitation.

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and development of novel therapeutics requires an understanding of pathophysiologic phenotypes.

Objectives: The purpose of the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study was to correlate clinical features and biomarkers with molecular characteristics in a well-profiled COPD cohort.

Methods: A total of 67 COPD subjects (forced expiratory volume in the first second of expiration [FEV]: 45%-80% predicted) and 63 healthy smoking and nonsmoking controls underwent multiple assessments including patient questionnaires, lung function, and clinical biomarkers including fractional exhaled nitric oxide (FENO), induced sputum, and blood.

Persistent respiratory effort after adenotonsillectomy in children with sleep-disordered breathing.

Objectives: Adenotonsillectomy (AT) markedly improves but does not necessarily normalize polysomnographic findings in children with adenotonsillar hypertrophy and related sleep-disordered breathing (SDB). Adenotonsillectomy efficacy should be evaluated by follow-up polysomnography (PSG), but this method may underestimate persistent respiratory effort (RE). Mandibular movement (MMas) monitoring is an innovative measurement that readily identifies RE during upper airway obstruction.

Mandibular Movements As Accurate Reporters of Respiratory Effort during Sleep: Validation against Diaphragmatic Electromyography.

Context: Mandibular movements (MM) are considered as reliable reporters of respiratory effort (RE) during sleep and sleep disordered breathing (SDB), but MM accuracy has never been validated against the gold standard diaphragmatic electromyography (EMG-d).

Objectives: To assess the degree of agreement between MM and EMG-d signals during different sleep stages and abnormal respiratory events.

Methods: Twenty-five consecutive adult patients with SDB were studied by polysomnography (PSG) that also included multipair esophageal diaphragm electromyography and a magnetometer to record MM.

Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations: A randomized controlled study.

Background: Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma.

Objective: We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157, on experimental HRV-16 inoculation in healthy subjects and asthmatic patients.

Perspectives on exhaled nitric oxide.

The history of nitric oxide (NO) in the respiratory field dates back to the beginning of the 1990s with the pioneering study by Lars Gustafsson et al describing the presence of endogenous NO in the exhaled breath of human beings. Soon after, independent studies showed that exhaled NO concentrations (FNO) is higher in asthmatics than in normal subjects. Not all asthmatics demonstrate a high FNO, reflecting the heterogeneity of asthma.

Monitoring mandibular movements to detect Cheyne-Stokes Breathing.

Background: The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with "sharp" large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM patterns. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard.

Exhaled Nitric Oxide in Systemic Sclerosis Lung Disease.

. Exhaled nitric oxide (eNO) is a potential biomarker to distinguish systemic sclerosis (SSc) associated pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We evaluated the discriminative validity, feasibility, methods of eNO measurement, and magnitude of differences across lung diseases, disease-subsets (SSc, systemic lupus erythematosus), and healthy-controls.

Mandibular position and movements: Suitability for diagnosis of sleep apnoea.

Background And Objective: Mandibular movements (MMs) and position during sleep reflect respiratory efforts related to increases in upper airway resistance and micro-arousals. The study objective was to assess whether MM identifies sleep-disordered breathing (SDB) in patients with moderate to high pre-test probability.

Methods: This was a prospective study of 87 consecutive patients referred for an in-laboratory sleep test.

Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study.

Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED.

Longitudinally Stable, Clinically Defined Clusters of Patients with Asthma Independently Identified in the ADEPT and U-BIOPRED Asthma Studies.

Background: ADEPT (Airways Disease Endotyping for Personalized Therapeutics) and U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome Consortium) are independent asthma biomarker studies that aim to enable personalization of therapies.

Methods: Patients in both studies were identified by similar criteria, and similar clinical parameters and biomarkers were assessed in blood, sputum, and airway samples. Fuzzy partition-around-medoid clustering was performed on the ADEPT dataset (n = 154) and independently on the U-BIOPRED asthma dataset (n = 82), filtered to match ADEPT inclusion criteria.

Utility of animal and in vivo experimental infection of humans with rhinoviruses in the development of therapeutic agents for viral exacerbations of asthma and chronic obstructive pulmonary disease.

There is an association with acute viral infection of the respiratory tract and exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Although these exacerbations are associated with several types of viruses, human rhinoviruses (HRVs) are associated with the vast majority of disease exacerbations. Due to the lack of an animal species that is naturally permissive for HRVs to use as a facile model system, and the limitations associated with animal models of asthma and COPD, studies of controlled experimental infection of humans with HRVs have been used and conducted safely for decades.

Alpha-1-antitrypsin inhibits nitric oxide production.

NO is an endogenously produced gas that regulates inflammation, vascular tone, neurotransmission, and immunity. NO production can be increased by exposing cells to several endogenous and exogenous proinflammatory mediators, including IFN-γ, TNF-α, IL-1β, and LPS. As AAT has been shown to inhibit cell activation and suppress cytokine production associated with proinflammatory stimulation, we examined AAT for NO-suppressive function.

Exhaled nitric oxide in pulmonary diseases: a comprehensive review.

The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be monitored easily in exhaled air. It is now possible to estimate the predominant site of increased fraction of exhaled NO (FeNO) and its potential pathologic and physiologic role in various pulmonary diseases. In asthma, increased FeNO reflects eosinophilic-mediated inflammatory pathways moderately well in central and/or peripheral airway sites and implies increased inhaled and systemic corticosteroid responsiveness.

Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma.

Introduction: Central airway nitric oxide flux (J'(awNO)) and peripheral airway/alveolar nitric oxide concentration (C(ANO)) during asthma exacerbation has not been investigated after correction for axial NO back-diffusion.

Methods: After measuring exhaled NO (fraction of exhaled nitric oxide (F(E)NO); ppb) at 50, 100, 150 and 200 ml/s, J'(awNO) (nl/s) and C(ANO) (ppb) were calculated using the two-compartment model and corrected for axial NO back-diffusion. Fifteen (8 males), non-smoking, patients with moderate-to-severe treated (inhaled corticosteroid (ICS) and inhaled long-acting beta(2)-agonist (LABA)) asthma, age 57+/-13 years (mean+/-SD), were studied at baseline, during exacerbation prior to oral corticosteroid, and during recovery after an 8 day tapering prednisone course.

Efficacy and tolerability of budesonide/formoterol in one hydrofluoroalkane pressurized metered-dose inhaler in patients with chronic obstructive pulmonary disease: results from a 1-year randomized controlled clinical trial.

Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.

Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.