Follow-Up and Management of Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia: Review and Experience of Our Reference Centers.

Chronic rhinosinusitis is the foremost manifestation in adult patients with primary ciliary dyskinesia (PCD). We present a retrospective series of 41 adult patients with a confirmed diagnosis of PCD followed in our reference centers. As part of the diagnostic work up in our centers, sinus computed tomography scans (CTs) are systematically performed. All patients also undergo a sampling of purulent secretions sampled from the middle meatus under endoscopic view for bacteriological analysis. In our series, CT opacities were consistent in all the patients, as well as mainly partial and located in ethmoid cells (100% of patients) and in maxillary sinuses (85.4% of patients), and stayed stable over time. In the 31 patients who had purulent secretions, bacteriological culture showed at least one bacterium in 83.9% (n = 26). There was no significant difference in positive cultures for Pseudomonas aeruginosa in patients >40 years old versus those <40 (p = 0.17; Fisher). Surgical management was performed in only 19% of patients in order to improve sinonasal mechanical drainage. Our data support the hypothesis that the sinuses can be considered as a bacterial reservoir. From this retrospective study, we have introduced several changes into our routine clinical practice in our reference centers. Based on our analyses, medical and surgical treatments benefit from incorporating bacteriological information and sinonasal symptoms much more than CT scan evaluation alone. All patients now undergo systematically an annual simultaneous bacteriological sampling of the middle meatus and sputum to follow the relationship between ENT and lung disease and to help to antibiotic therapy strategy.

Critical Evaluation of Sinonasal Disease in 64 Adults with Primary Ciliary Dyskinesia.

To date, no study precisely described ear, nose and throat (ENT) disease in adults with primary ciliary dyskinesia (PCD) and its relationship with ciliary function/ultrastructure. A retrospective study of standardized ENT data (exam, audiogram, sinus Computed tomography (CT), and bacteriology) was conducted in 64 adults with confirmed PCD who were followed in two ENT reference centers. Rhinorrhoea and hearing loss were the main symptoms. Symptom scores were higher in older patients. Nasal endoscopy was abnormal in all patients except one, showing nasal polyps in one-third of the patients and stagnant nasal mucus secretions in 87.5% of the patients. Sinus CT opacities were mainly incomplete and showed one-third of the patients with sinus hypoplasia and/or agenesis. Middle meatus mainly grew Haemophilus influenzae, Streptoccocus pneumoniae and Pseudomonas aeruginosa. Otitis media with effusion (OME), which is constant in childhood, was diagnosed in less than one-quarter of the patients. In two-thirds of the patients, audiogram showed hearing loss that was sensorineural in half of the patients. ENT disease severity was not correlated with ciliary function and ultrastructure, but the presence of OME was significantly associated with a forced expiratory volume (FEV1) < 70%. Rhinosinusitis is the most common clinical feature of PCD in adults, while OME is less frequent. The presence of active OME in adults with PCD could be a severity marker of lung function and lead to closer monitoring.

Nasal response to stress test in healthy subjects: an experimental pilot study.

PURPOSE: Stress has been suspected to play a role in rhinitis. The role of stress on nasal patency has been not yet elucidated. The aim was to evaluate the potential effects of stress on nasal patency in healthy subjects. METHODS: We conducted a prospective pilot study including 12 healthy subjects. Experimental protocol was divided in three periods (pre-task, task and recovery). In the task period, subjects were exposed to the "Trier Social Stress Test" (TSST), a standardized laboratory stressor. Different parameters including Spielberger State Anxiety Inventory (SSAI) score, visual analogic scale (VAS) of nasal patency feeling, heart rate, acoustic rhinometry measurements have been compared between the three different periods. The study population was divided into two groups according to the Spielberger Trait Anxiety Inventory (STAI) score: A "non anxious" group and a "weakly anxious" group. RESULTS: Seven subjects were in the "non anxious" group and five in the "weakly anxious" group. TSST significantly increased heart rate in all volunteers. SSAI score was significantly increased (p = 0.04) after the task period (36.6 ± 11.3) when compared to the SSAI score in pre-task period (31.9 ± 12.6). VAS score of nasal patency feeling significantly decreased from pre-task to task and recovery periods. Mean minimal cross-sectional areas and mean volumes of the nasal cavities were not significantly different between the three periods, except in "weakly anxious" group, but the small number of subjects does not allow to draw a definite conclusion. CONCLUSION: We observed that stress influenced the feeling of nasal patency in healthy subjects. However, the objective effects of stress on nasal geometry were globally non-significant except in "weakly anxious" group. This latter result of our pilot study needs to be confirmed in a larger cohort.

Investigating hyperventilation syndrome in patients suffering from empty nose syndrome.

OBJECTIVES/HYPOTHESIS: Patients with empty nose syndrome (ENS) following turbinate surgery often complain about breathing difficulties. We set out to determine if dyspnea in patients with ENS was associated with hyperventilation syndrome (HVS). We hypothesized that lower airway symptoms in ENS could be explained by HVS. STUDY DESIGN: Observational prospective study. METHODS: All consecutive patients referred to our center for ENS over 1 year were invited to participate. Patients completed the Nijmegen score and underwent a hyperventilation provocation test (HVPT) and arterial blood gas and cardiopulmonary tests. HVS was defined by a delayed return of the end-tidal partial pressure of carbon dioxide in the expired gas to baseline during HVPT. Patients with HVS were asked to complete the Sinonasal Outcome Test (SNOT)-16 questionnaire before and after a specific eight-session respiratory rehabilitation program. RESULTS: Twenty-two of the 29 patients referred for ENS during the study period were eligible for inclusion and underwent a complete workup. HVS was diagnosed in 17 of these patients (77.3%). In the five patients who completed the SNOT-16, the score was significantly lower after rehabilitation. CONCLUSIONS: This study suggests that HVS is frequent in patients with ENS, and that symptoms can be improved by respiratory rehabilitation. Pathophysiological links between ENS and HVS deserve to be further explored. LEVEL OF EVIDENCE: 2b Laryngoscope, 127:1983-1988, 2017.

A functional tool to differentiate nasal valve collapse from other causes of nasal obstruction: the FRIED test.

Nasal valve collapse is a dynamic abnormality that is currently diagnosed purely on the basis of clinical features and thus subject to certain interpretation. The aim of this study was to develop a new and reliable functional test to objectively characterize nasal valve collapse. This was an observational prospective study including consecutive patients referred to our center for exploration of chronic nasal congestion. The patients were classified into two groups according to their symptoms and clinical abnormalities: the nasal valve collapse (NV+) group when nasal valve collapse was clinically detected during moderate forced inspiration and/or when the feeling of nasal congestion improved during passive nasal lateral cartilage abduction (n = 32); and the no-nasal valve collapse (NV-) group for the others (n = 23). All patients underwent nasal functional tests (posterior rhinomanometry and acoustic rhinometry) before and after topical nasal decongestion. We compared the difference between the pressure flow of the inspiratory and expiratory phases during posterior rhinomanometry [flow rate inspiratory-expiratory difference (FRIED) test] between the two groups. The difference between the absolute value of inspiratory and expiratory flow was significantly higher in the NV+ group than in the NV- group both before and after topical decongestion. The cutoff value for the FRIED test was -0.008 l/s with a good sensitivity (82%) and a specificity of 59%. We suggest that the FRIED test constitutes an objective and easy-to-apply technique to diagnose nasal valve collapse in daily practice.

Quantitative analysis of ciliary beating in primary ciliary dyskinesia: a pilot study.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained. We postulated that a quantitative analysis of beat pattern would improve PCD diagnosis. We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded. METHODS: Nasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD. In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges. The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the "gold standard" used to establish the diagnosis of PCD. RESULTS: This "gold standard" excluded PCD in 15 patients (non-PCD patients), confirmed PCD in 10 patients (PCD patients) and was inconclusive in 9 patients. Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity. Qualitative evaluation and quantitative analysis were concordant in non-PCD patients. In 9/10 PCD patients, quantitative analysis was concordant with the "gold standard", while the qualitative evaluation was discordant with the "gold standard" in 3/10 cases. Among the patients with an inconclusive "gold standard", the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease-causing mutations in one patient) and PCD exclusion in 2/9 patients. CONCLUSIONS: When the beat pattern is normal or virtually immotile, the qualitative evaluation is adequate to study ciliary beating in patients suspected for PCD. However, when cilia are still beating but with moderate alterations (more than 40% of patients suspected for PCD), quantitative analysis is required to precise the diagnosis and can be proposed to select patients eligible for TEM.

Airway responsiveness measured by forced oscillation technique in severely obese patients, before and after bariatric surgery.

BACKGROUND: The influence of obesity on airway responsiveness remains controversial. OBJECTIVE: This study was designed to investigate airway responsiveness, airway inflammation, and the influence of sleep apnea syndrome (SAS), in severely obese subjects, before and after bariatric surgery. METHODS: A total of 120 non-asthmatic obese patients were referred consecutively for pre-bariatric surgery evaluation. Lung function, airway responsiveness to methacholine, exhaled nitric oxide measurement, and sleep studies were performed. Airway hyperresponsiveness (AHR) was defined as a 50% or greater increase in respiratory resistance measured using the forced oscillation technique in response to a methacholine dose ≤ 2000 µg. Forced expiratory volume in 1 second (FEV1) was measured after the last methacholine dose. Airway responsiveness was reevaluated after weight loss in patients with a pre-surgery AHR. RESULTS: AHR was found in 16 patients. The percent FEV1 decrease or percent respiratory resistance increase in response to methacholine was related to baseline expiratory airflow (forced expiratory flow at 50%) (r = 0.26, p < .006 and r = 0.315, p = .0005, respectively) but not to body mass index (BMI) or exhaled nitric oxide. Both airway responsiveness parameters were significantly related to forced expiratory flow at 25-75%/forced vital capacity, a measure of airway size relative to lung size (r = 0.27, p < .005 and r = 0.25, p < .007, respectively). Sleep apnea was not significantly associated with AHR or airway inflammation. About 11 patients with AHR were reevaluated 18 months to 2 years after surgery, with no change in AHR associated with weight loss. CONCLUSION: Airway responsiveness is not related to BMI or to SAS. AHR in severely obese patients might be related to distal airway obstruction or low relative airway size.

Polypectomy compared with ethmoidectomy in the treatment of nasal polyposis.

OBJECTIVE: To compare the 3-year results of 2 endoscopic surgical approaches in the management of nasal polyposis. DESIGN: Retrospective medical record review. SETTING: Private or institutional practice. PATIENTS: A total of 127 patients with nasal polyposis were operated on by the same surgeon between January 1, 2003, and September 31, 2005. INTERVENTION: The patients underwent radical ethmoidectomy (n = 77) and polypectomy (n = 50). MAIN OUTCOME MEASURES: Outcome measures were global functional score, calculated by summing the scores (0-3) of each symptom (congestion, rhinorrhea, anosmia, hyperreactivity, and pain); global anatomical score (GAS), calculated by summing the score of polyp development for each nasal cavity; computed tomography score; adherence to corticosteroid therapy; oral corticosteroid consumption; and complication and subsequent operation rate. Efficacy was evaluated by comparing these data preoperatively and postoperatively (at 3 months, 1 year, and 3 years). RESULTS: The global functional score and GAS were significantly improved 3 years after these techniques were performed (global functional score changes from 8.65 to 3.11 for ethmoidectomy and from 8.15 to 4.2 for polypectomy; GAS, from 5.95 to 1.83 for ethmoidectomy and from 6.57 to 3.58 for polypectomy). Congestion, pain, and GAS were improved to a significantly greater extent in the ethmoidectomy group. The subsequent operation rate for symptomatic polyp recurrence was comparable (9.1% vs 8.0%), with fewer local complications in the polypectomy group. CONCLUSION: Polypectomy seems to represent a valuable alternative in the armamentarium of first-hand surgical procedures for treating nasal polyposis.

Offline exhaled nitric oxide in emergency department and subsequent acute asthma control.

BACKGROUND: Few studies have evaluated exhaled NO measurement during acute asthma. OBJECTIVES: To evaluate exhaled NO fraction (FE(NO)) and peak expiratory flow (PEF) time-courses during acute asthma treatment (beta 2-agonist plus systemic steroid) and to assess whether FE(NO) time-course predicts subsequent asthma control. METHODS: Sixty-five asthmatic patients (mean +/- SD, 34 +/- 10 years) were prospectively enrolled in three Emergency Departments. RESULTS: Sixteen patients were excluded (failure of offline FE(NO) measurement at 100 mL/s [FE(NO 0.1)], n = 4, and early discharge). The 49 remaining patients performed FE(NO 0.1) and PEF on admission, at the 2nd (H2) and 6th hour (H6). Follow-up using an Asthma Control Diary was obtained in 27 of 49 patients, whether they were hospitalized (n = 9) or discharged (n = 18). All but 2 patients had elevated FE(NO) on admission (median [interquartile], 49 [26-78] ppb). Unlike PEF, mean FE(NO 0.1) of our sample was not significantly modified by treatment. No significant relationship was evidenced between exhaled NO and PEF variations. The variation of FE(NO 0.1) [H0 minus H6] was different in patients who were hospitalized (decrease of 8 +/- 20 ppb) versus discharged (increase of 5 +/- 20 ppb, p = 0.04). This variation of FE(NO 0.1) was correlated with the Diary score (control of subsequent week), an initial increase in FE(NO 0.1) being associated with better asthma control. Nevertheless, neither exhaled NO nor PEFR were good predictors of asthma control. CONCLUSIONS: An increase in FE(NO) is observed in almost all patients with acute asthma, and its subsequent increase within 6 hours is associated with a better degree of asthma control in the subsequent week.

Impairment of nitric oxide output of conducting airways in primary ciliary dyskinesia.

Nasal nitric oxide (NO) concentration is dramatically reduced in primary ciliary dyskinesia (PCD). The aims of this study were to apply a multiple-flow NO analysis to investigate whether NO output from the bronchial tree was affected in a similar way to nasal NO output, and to search for a relationship between flow-independent exchange parameters and airflow limitation. Multiple flow rate analysis of exhaled NO, allowing the calculation of maximum airway wall flux and alveolar NO concentration, was performed in 17 PCD patients (median age, 25-75th percentiles: 13.5, 12.1-17.6) with documented ultrastructural cilia abnormalities and 28 healthy subjects (16.0, 11.0-21.0). Median maximum airway wall flux and median alveolar NO concentration were significantly reduced in PCD patients compared to healthy subjects: 16.0, 7.5-29.5, vs. 25.0, 15.0-32.5 nl/min (P<0.05) and 2.5, 1.6-3.3, vs. 5.0, 3.6-6.5 ppb (P<0.01), respectively. Significant correlations between maximum airway wall flux and airflow limitation were found, i.e., resistance of respiratory system (rho=0.74, P<0.005), forced expiratory volume in one second (FEV(1))/VC (rho= -0.61, P<0.05), FEV(1) (rho=-0.52, P< 0.05), mid expiratory flow between 25 and 75% of forced vital capacity (MEF(25-75)) (rho=-0.54, P<0.05), and maximal instantaneous expiratory flow at 50% of the vital capacity (MEF(50)) (rho=-0.55, P<0.05). In conclusion, the impairment of NO output is less pronounced in the lower than in the upper (nasal) respiratory tract in PCD. A decrease in maximal NO output from conducting airways is associated with limited airflow impairment.

Validity criteria and comparison of analytical methods of flow-independent exhaled NO parameters.

The objective was to assess both validity and comparability of multiple constant (MCF, mainly performed) and dynamically changing (DCF, new method) flow analyses calculating alveolar concentration (Calv(NO)), maximum conducting airway flux (J'aw(NO)) and airway diffusing capacity (Daw(NO)) of exhaled NO (FE(NO)). (Calv(NO), J'aw(NO))(R) where R is the correlation coefficient of the linear regression between NO output and expiratory flow rate (MCF) and (Calv(NO), J'aw(NO), Daw(NO))(Delta100) where Delta100 is the ratio ([observed-predicted FE(NO)]/observed FE(NO)) at 100 ml/s (DCF) were assessed in 18 healthy subjects (10 atopic). MCF demonstrated a linear relationship (R > or = 0.80) between NO output and expiratory flow in 15/18 subjects. DCF was valid (Delta100 < or = 30%) in 12/18 subjects. A good agreement between MCF and DCF was evidenced in the nine subjects with R > or = 0.80 and Delta100 < or = 30%. Failure of validity criteria was mainly observed in atopic subjects. In conclusion, when validity criteria are satisfied, the new DCF method similarly characterizes NO exchange parameters than MCF approach.

Nasal wall compliance in vasomotor rhinitis.

Nasal compliance is a measure related to the blood volume in the nasal mucosa. The objective of this study was to better understand the vascular response in vasomotor rhinitis by measuring nasal cross-sectional area and nasal compliance before and after mucosal decongestion in 10 patients with vasomotor rhinitis compared with 10 healthy subjects. Nasal compliance was inferred by measuring nasal area by acoustic rhinometry at pressures ranging from atmospheric pressure to a negative pressure of -10 cmH2O. Mucosal decongestion was obtained with one puff per nostril of 0.05% oxymetazoline. At atmospheric pressure, nasal cross-sectional areas were similar in the vasomotor rhinitis group and the healthy subject group. Mucosal decongestion did not induce any decrease of nasal compliance in patients with vasomotor rhinitis in contrast with healthy subjects. Our results support the hypothesis, already proposed, of an autonomic dysfunction based on a paradoxical response of the nasal mucosa in vasomotor rhinitis. Moreover, the clearly different behavior between healthy subjects and vasomotor rhinitis subjects suggests that nasal compliance measurement may therefore represent a potential line of research to develop a diagnostic tool for vasomotor rhinitis, which remains a diagnosis of exclusion.

Factors associated with dyspnea in adult patients with sickle cell disease.

OBJECTIVE: The aim of this prospective study was to determine the cardiorespiratory factors associated with dyspnea in patients with sickle cell SS-hemoglobin disease, with a specific interest in lung vascular involvement. MEASUREMENTS: Forty-nine patients (29 women and 20 men; mean [+/- SD] age: women, 29 +/- 6 years; men, 31 +/- 11 years) underwent direct evaluations (Borg scale evaluation during a 6-min walk test) and indirect evaluations (modified Medical Research Council [MRC]score) of their dyspnea, pulmonary function tests (PFTs) [spirometry, volumes, diffusing capacity of the lung for carbon monoxide (Dlco), diffusing capacity of the alveolar-capillary membrane, and pulmonary capillary blood volume measurements], echocardiography, and biological evaluation. RESULTS: Thirty-four patients complained of significant breathlessness (MRC score, > 1). Indirect and direct evaluations of dyspnea were correlated. PFT results depicted a very mild restrictive pattern (mean total pulmonary capacity, 86 +/- 11% predicted) and an impairment of Dlco (mean Dlco corrected for the degree of anemia, 69 +/- 13% predicted). The statistical analysis demonstrated that dyspnea and exercise performance were closely linked to indexes of Dlco but not with any echocardiographic or biological measure including anemia. Nevertheless, only approximately 25% of the variability was explained by these associations. Despite having a similar history of vasoocclusive crisis events, women had more severe anemia, dyspnea, decreases in Dlco (corrected for the degree of anemia), and a higher capillary blood volume (corrected for alveolar volume) than men. CONCLUSION: Lung vascular disease contributes to dyspnea and the exercise limitation of patients with sickle cell disease. A sequential assessment of Dlco would therefore constitute one of the objective functional end points for follow-up studies of these patients.

Alveolar nitric oxide and effect of deep inspiration during methacholine challenge.

STUDY OBJECTIVES: To assess whether the dual anatomic origin of exhaled nitric oxide (NO), namely alveolar and bronchial, could explain the link between exhaled NO and airway responsiveness, and could participate in the bronchodilatory effect of deep inspiration (DI) that may be evidenced during methacholine challenge. DESIGN AND SETTING: Prospective study in a laboratory performing pulmonary function tests of an academic hospital. PATIENTS AND INTERVENTIONS: Patients underwent multiple flow analysis of exhaled NO, allowing calculation of total maximum airway NO flux (J'awno) and NO concentration of expansible compartment (CAno), and received a cumulative methacholine dose of 2,000 microg. DI effect was assessed by continuous measurement of the resistance of respiratory system using the forced oscillation technique before and after DI. RESULTS: In a first phase involving 23 patients, a positive correlation between log values of J'awno and CAno was demonstrated with the degree of airway responsiveness (percentage of FEV(1) decrease). In a second phase involving 38 patients, only log CAno was correlated with responsiveness, and no significant relationship was demonstrated between J'awno or CAno and the effect of DI. Patients with smaller airways and/or distal airflow limitation exhibited a constrictive response to DI. CONCLUSION: Airway responsiveness is mainly associated with an increase in distal origin of NO output, and no relationship between exhaled NO and the effect of DI was evidenced.

Perceived inspiratory difficulty in neuromuscular patients with primary muscle disorders.

Intensity of perceived inspiratory difficulty was investigated in 17 patients with severe respiratory insufficiency due to muscle disease, compared with healthy matched controls. Subjects breathed through a threshold valve generating a constant inspiratory negative pressure proportional to their maximal inspiratory pressure. Four load levels ranging from 10 to 40% of the maximal inspiratory pressure were applied in random order. Patients had significantly less perceived inspiratory difficulty than controls at each load level expressed as a percentage of maximal inspiratory pressure P < 0.001. However, when the load was expressed as the absolute value, the slope of the Borg scale score versus mouth pressure was similar in the two groups (P = 0.11). The ventilatory pattern remained unchanged in each group as the load increased. We conclude that in patients with myopathy, loads leading to respiratory muscle fatigue (40% of maximal inspiratory pressure) may fail to produce perceived inspiratory difficulty.

Increase in alveolar nitric oxide in the presence of symptoms in childhood asthma.

STUDY OBJECTIVES: To determine respective contributions of alveolar and proximal airway compartments in exhaled nitric oxide (NO) output (QNO) in pediatric patients with asthma and to correlate their variations with mild symptoms or bronchial obstruction. PATIENTS AND DESIGN: In 15 asthmatic children with recent mild symptoms, 30 asymptomatic asthmatic children, and 15 healthy children, exhaled NO concentration was measured at multiple expiratory flow (V) rates allowing the calculation of alveolar and proximal airway contributions in QNO, using two approaches, ie, linear and nonlinear models. MEASUREMENTS AND RESULTS: Asymptomatic and recently symptomatic patients were not significantly different regarding FEV(1) and maximum V between 25% and 75% of FVC (MEF(25-75)): FEV(1), 93.3 +/- 13.4% vs 90 +/- 7.5%; MEF(25-75), 70 +/- 22% vs 68 +/- 28% of predicted values, respectively (mean +/- SD). Maximal airway QNO output was significantly higher in recently symptomatic vs asymptomatic patients (p < 0.0001), and in asymptomatic patients vs healthy children (p < 0.02): 134 +/- 7 nl/min, 55 +/- 43 nl/min, and 19 +/- 8 nl/min, respectively. In a multiple regression analysis, variables that influenced airway QNO output were symptoms (p < 0.0001) and distal airway obstruction as assessed by MEF(25-75) (p < 0.05). Alveolar NO concentration (FANO) was significantly (p < 0.03) higher in recently symptomatic than in patients without symptoms, whereas it was not significantly different between asymptomatic patients and healthy children: 7.2 +/- 2.4 parts per billion (ppb), 5.5 +/- 2.7 ppb, and 4.2 +/- 2.0 ppb, respectively. CONCLUSIONS: An increase in FANO was observed in the presence of symptoms, and proximal airway NO output was correlated with distal obstruction during asthma.

Both inflammation and remodeling influence nitric oxide output in children with refractory asthma.

BACKGROUND: Exhaled nitric oxide can be used to monitor airway inflammation in asthma. We hypothesized that the strong link between nitric oxide and inflammation may obscure a weaker link with airway remodeling. OBJECTIVE: The aim of this study was to determine whether airway remodeling influenced exhaled nitric oxide in 28 asthmatic children (median age [25th-75th], 11 [10-14] years old) with refractory asthma defined as airflow limitation and/or exacerbations despite high-dose inhaled steroids. METHODS: Multiple-flow analysis of exhaled nitric oxide was used to correlate alveolar nitric oxide concentration and maximal conducting airway nitric oxide output to pulmonary function tests, bronchoalveolar lavage, and bronchial biopsy findings. RESULTS: Nitric oxide measurements were related to inflammation and T(H)1/T(H)2 balance, that is, subepithelial eosinophilic infiltration and eosinophilic cationic protein and IFN-gamma/IL-4 ratio in bronchoalveolar lavage fluids. Nitric oxide measurements were also correlated with several parameters of airway remodeling: alveolar nitric oxide concentration with TGF-beta in bronchoalveolar lavage fluid (r = 0.42, P =.03) and maximal conducting airway nitric oxide output with reticular basement membrane thickness (r = 0.61, P =.0007) and tissue inhibitor of matrix metalloproteinases 1/matrix metalloproteinase 9 ratio in bronchoalveolar lavage fluid (r = 0.43, P =.04). Moreover, alveolar nitric oxide concentration was correlated with MEF(25-75) (r = 0.60, P =.02). CONCLUSIONS: These findings suggest that both subacute inflammation and remodeling influence nitric oxide output in refractory asthma.

Comparative effects of two ventilatory modes on speech in tracheostomized patients with neuromuscular disease.

Many patients with respiratory failure related to neuromuscular disease receive chronic invasive ventilation through a tracheostomy. Improving quality of life, of which speech is an important component, is a major goal in these patients. We compared the effects on breathing and speech production of assist-control ventilation (ACV) and bilevel positive-pressure ventilation (BPPV) in nine patients with neuromuscular disease. Ventilator-delivered flow was measured using a pneumotachograph, and respiratory rate, inspiratory time, and ventilator-delivered volume were measured on this flow signal. Gas exchange was assessed using oxygen saturation and end-tidal carbon dioxide measurement. Microphone speech recordings were subjected to quantitative analysis. At rest, ventilatory parameters were similar with both modes. Speech induced an increase in inspiratory time during BPPV, with a greater increase in the volume released by the ventilator during speech as compared with ACV (172 +/- 194 versus 26 +/- 31 ml). Consequently, speech duration was longer during inspiration with BPPV. Moreover, BPPV allowed speech production to extend into expiration, and three patients could speak continuously during several respiratory cycles while receiving BPPV. Blood gas exchange was not modified by speech with BPPV or ACV. This study shows that BPPV provides better speech duration than ACV with no detectable short-term deleterious effects.

Increased nitric oxide output from alveolar origin during liver cirrhosis versus bronchial source during asthma.

The aim of this study was to assess the usefulness of nitric oxide (NO) output measurement at multiple expiratory flow rates during diseases characterized by increased exhaled NO (FE(NO)) that could come from alveolar (liver cirrhosis) or bronchial (asthma) sources. It has been proposed that NO output measurements expressed as a function of expiratory flow allow alveolar NO concentration (FA(NO)) and maximal bronchial NO output (Qbr,max (NO)) to be computed. In 36 healthy nonsmoking subjects, we found that maximal bronchial NO output (37 +/- 3 nl/min) was correlated with the height of the subjects (p = 0.02). Alveolar NO concentration was 5.1 +/- 0.3 (SEM) ppb, which represented 31 +/- 2% and 61 +/- 3% of FE(NO) at 50 and 200 ml/s expiratory flow rate, respectively. Nonsmoking subjects with asthma (n = 28) were characterized by an increase in Qbr,max (NO) (133 +/- 14 nl/min) as compared with healthy nonsmoking subjects (p < 0.0001). FE(NO)50, FE(NO)200, and Qbr,max (NO) were equally efficient in differentiating subjects with asthma from healthy subjects. Patients with liver cirrhosis (n = 26, 14 smokers and 12 nonsmokers) had an increased FA(NO) compared with healthy subjects (cirrhosis: 8.3 +/- 0.9 ppb, healthy nonsmokers [n = 36] and smokers [n = 20], n = 56: 4.7 +/- 0.3 ppb, p < 0.05), which was correlated with the alveolar-arterial oxygen difference (p = 0.007). FA(NO) and FE(NO)200, but not FE(NO)50 values, allowed patients with liver cirrhosis to be differentiated from healthy subjects. These results suggest that a two-compartment model for NO output allows the increase in FE(NO) from alveolar sources to be differentiated from the increase from bronchial sources.