Cannabis-Associated Asthma and Allergies.

Inhalation of cannabis smoke is its most common use and the pulmonary complications of its use may be the single most common form of drug-induced pulmonary disease worldwide. However, the role of cannabis consumption in asthma patients and allergic clinical situations still remains controversial. To review the evidence of asthma and allergic diseases associated with the use of marijuana, we conducted a search of English, Spanish, and Portuguese medical using the search terms asthma, allergy, marijuana, marihuana, and cannabis. Entries made between January 1970 and March 2017 were retrieved. Several papers have shown the relationship between marijuana use and increase in asthma and other allergic diseases symptoms, as well as the increased frequency of medical visits. This narrative review emphasizes the importance to consider cannabis as a precipitating factor for acute asthma and allergic attacks in clinical practice. Although smoking of marijuana may cause respiratory symptoms, there is a need for more studies to elucidate many aspects in allergic asthma patients, especially considering the long-term use of the drug. These patients should avoid using marijuana and be oriented about individual health risks, possible dangers of second-hand smoke exposure, underage use, safe storage, and the over smoking of marijuana.

Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: effects of inhaled beclomethasone.

There is controversy about the role of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). Although they appear to have little impact on airways obstruction or its progression, their use may reduce the frequency and/or severity of exacerbations in a subset of patients. We undertook the following study to determine the impact of inhaled corticosteroid on two noninvasive markers of airways inflammation. We assigned 20 stable nonsmoking patients with COPD in random, double-blind crossover fashion to two 2-wk treatment periods with inhaled beclomethasone 500 microg twice daily or matching placebo, followed by a 2-wk washout period. We measured exhaled nitric oxide (ENO), breath condensate H(2)O(2), and flow volume spirometry at weekly intervals. Median baseline ENO was 26.2 (19.3 to 54.8) ppb and fell significantly following 1 and 2 wk of beclomethasone (-10.6 ppb, p = 0.002, and -6.3 ppb, p = 0.013, respectively) but was unchanged by placebo inhalation. Breath condensate H(2)O(2) levels did not change significantly with inhaled beclomethasone or placebo. Although there were no significant changes in FEV(1) with BDP therapy, there was a moderate inverse correlation between changes in ENO and changes in FEV(1) (r -0.50). We conclude that inhaled beclomethasone reduces ENO levels in stable nonsmoking patients with COPD, a finding compatible with an antiinflammatory mechanism of action.

Exhaled nitric oxide in chronic obstructive pulmonary disease: relationship to pulmonary function.

The following study was undertaken in order to determine how exhaled nitric oxide (eNO) levels in former smokers with chronic obstructive pulmonary disease (COPD) compared to eNO levels in patients with asthma and in healthy nonsmoking volunteers. The study also aimed to determine any relationship between eNO levels in COPD and: 1) conventional measures of lung function; and 2) inhaled corticosteroid (ICS) use. In former smokers with COPD, nonsmokers with asthma and volunteers, eNO levels, spirometry, lung volumes, carbon monoxide diffusion capacity of the lung (DL,CO) and resting oxygen saturation (Sa,O2) were measured. Median eNO was significantly higher among patients with COPD than among healthy volunteers (p = 0.003) but lower than among patients with asthma (p < 0.01). There was no significant difference in eNO levels between COPD patients using ICS and those not using ICS. By contrast, eNO was lower among asthma patients who used ICS (median 32 parts per billion (ppb); 25-75% range 16-54) than among asthma patients who did not (51 ppb; 32-87) (p = 0.034). Among patients with COPD, eNO was inversely correlated with forced expiratory volume in one second, DL,CO and Sa,O2, and was positively correlated with the residual lung volume/total lung capacity ratio. Among patients with asthma, no significant correlations were found. Exhaled nitric oxide is increased in patients with chronic obstructive pulmonary disease, an increase that is influenced by structural abnormalities of tobacco-induced lung damage.

Lung function 5 yr after lung volume reduction surgery for emphysema.

Current datum more than 2 yr after lung volume reduction surgery (LVRS) for emphysema is limited. This prospective study evaluates pre-LVRS baseline and 5-yr results in 26 symptomatic patients (mean age 67 +/- 6 yr) (mean +/- SD) who underwent bilateral, targeted upper lobe stapled LVRS using video-assisted thoracoscopy. Baseline forced expiratory volume in 1 s (FEV(1)) was 0.7 +/- 0.2 L (mean +/- SD), 29 +/- 10% predicted. Following LVRS, with none lost to follow-up, mortality due to respiratory failure at 0.5, 1, 2, 3, 4, and 5 yr was 4%, 4%, 19%, 31%, 46%, and 58%, respectively. Increase above baseline for FEV(1) > 200 ml and/or FVC > 400 ml at 1, 2, 3, 4, and 5 yr post-LVRS was noted in 73%, 46%, 35%, 27%, and 8% of all patients; decrease in dyspnea grade >/= 1 in 88%, 69%, 46%, 27%, and 15%; and elimination of initial oxygen dependence in 18 patients in 78%, 50%, 33%, 22%, and 0%, respectively. Expiratory airflow improved due to the increase in both lung elastic recoil and small airway intraluminal caliber. Five patients decreased FEV(1) 141 +/- 60 ml/yr and FVC 102 +/- 189 ml/yr over 3.8 +/- 1.2 yr post-LVRS, similar to their pre-LVRS rate of decline. In the 11 patients who survived 5 yr, at 0.5-1.0 yr post-LVRS peak increase in FEV(1) was 438 +/- 366 ml, with a decline of 149 +/- 157 ml the following year and 78 +/- 59 ml/yr over 4.0-4.5 yr. Bilateral LVRS provided palliative clinical and physiological improvement in 9 of 26 patients at 3 yr, 7 at 4 yr, and 2 at 5 yr.

Dose-response relationship and reproducibility of the fall in exhaled nitric oxide after inhaled beclomethasone dipropionate therapy in asthma patients.

STUDY OBJECTIVES: The fractional concentration of exhaled nitric oxide (FENO) is a marker of asthmatic airway inflammation. We determined the dose response and the reproducibility of the FENO fall following inhaled beclomethasone dipropionate (iBDP) therapy in nonsteroid-treated asthmatic patients. STUDY DESIGN: Study A: For four 1-week periods (period 1 to period 4), the following regimens were administered in sequential order to 15 nonsteroid-treated asthmatic patients: period 1, placebo; period 2, 100 microg/d of iBDP; period 3, 400 microg/D of iBDP; and period 4, 800 microg/d of iBDP. Spirometry, FENO, and provocative concentration of methacholine resulting in a 20% fall in FEV(1) (PC(20)) were measured at each of five visits (visit 1 to visit 5). Study B: During four periods, 12 nonsteroid-treated asthmatic patients received placebo treatment for 7 days (period 1), 200 microg/d of iBDP for 14 days (period 2), washout on placebo treatment until the FENO was within 15% of baseline (period 3), and 200 microg/d of iBDP for 14 days (period 4). RESULTS: Study A: Mean FEV(1) rose progressively from 3.10 L (visit 1) to 3.41 L (visit 5; p = 0.001). All iBDP doses caused a significant FEV(1) rise compared to placebo treatment, but with no significant separation of doses using FEV(1). FENO geometric mean (95% confidence limits) fell progressively from 103.5 parts per billion (ppb) (78.5 to 136.7) to 37.4 ppb (29.1 to 48.0) from visit 1 to visit 5 (p = 0.001). All doses of iBDP resulted in a significant change in FENO from placebo treatment, but with significant separation of only the 100-microg and 800-microg doses by FENO. Geometric mean (95% confidence limits) PC(20) rose progressively from 0.01 mg/mL (0.00 to 0.19) to 0.48 mg/mL (0.01 to 8.1) from visit 1 to visit 5 (p = 0.002). All doses of iBDP resulted in a significant change in PC(20) from baseline or placebo treatment, but with no significant separation of active iBDP doses using PC(20). Study B: FENO fell from 111.56 ppb (80.3 to 155.1) to 66.3 ppb (49.2 to 89.5; p < 0.001) from period 1 to period 2, and from 110.2 ppb (79.3 to 153.1) to 61.7 ppb (42.9 to 88.8; p < 0.001) from period 3 to period 4. There were no significant differences between FENO in period 1 and period 3 (p = 0.83) or between period 2 and period 4 (p = 0.220). CONCLUSIONS: FENO was superior to FEV(1) and PC(20) in separating doses of iBDP. The fall in FENO after two identical administrations of iBDP separated by placebo washout was highly reproducible.

Unsuspected pseudophysiologic emphysema in chronic persistent asthma.

The current literature emphasizes the role of airway remodeling in chronic persistent asthma and its putative effect on causing fixed expiratory airflow limitation. We studied 18 adults with chronic persistent asthma; 12 men, six women, age 59 +/- 15 yr (mean +/- SD) with fixed expiratory airflow obstruction. We measured lung elastic recoil and examined the mechanism of expiratory airflow limitation. Diaphragmatic strength was also measured in six asthmatics, using both sniff and partially occluded airway technique. All 18 asthmatics had markedly abnormal maximal expiratory flow-volume curves at both high and low lung volumes. Hyperinflation was present at residual volume (RV), FRC, and TLC in all subjects. Diffusing capacity was normal or elevated and lung computed tomography (CT) was normal in all 18 asthmatic subjects. There was a significant loss of lung elastic recoil in three of four asthmatics age 30 to 49, all five age 51 to 60 yr, and seven of nine age 61 to 82 yr. Maximal expiratory airflow limitation in only four elderly asthmatics and only at low lung volumes was due completely to loss of lung elastic recoil. In the others, we estimate the reduction in lung elastic recoil was responsible for 35% reduction in maximal expiratory airflow at 80% of TLC, and 55% at 70% of TLC. Despite hyperinflation, transdiaphragmatic pressures and strength were normal. The mechanisms responsible for loss of lung elastic recoil remain elusive. The high incidence of loss of lung elastic recoil in chronic persistent asthma was unexpected, and its contribution to abnormal lung function needs to be emphasized.

Unilateral nasal nitric oxide measurement after nasal surgery.

This study was designed to validate and standardize a method for unilateral nasal nitric oxide (NO) measurement. Fourteen healthy volunteers and 11 patients who had undergone unilateral medial maxillectomy were enrolled. Nasal NO was measured unilaterally by means of a dual pump system, and bilateral nasal NO was measured by aspirating air through the nasal airway in series. The median unilateral NO output was 195 nL/min on the surgical side and 291 nL/min on the contralateral, surgically untreated side (p = .006). The NO output was not significantly different between nostrils in the control group (p = .82). With the bilateral technique, there was no significant difference between the surgery group and the healthy-subjects group (p = .72). The unilateral nasal NO technique is sensitive in determining unilateral differences in nasal NO production. The NO outputs from the nostrils were similar in normal subjects regardless of the nasal cycle, but were significantly lower on the operated side in the unilateral nasal surgery group.

A new ventilator for monitoring lung mechanics in small animals.

Researchers investigating the genetic component of various disease states rely increasingly on murine models. We have developed a ventilator to simplify respiratory research in small animals down to murine size. The new ventilator provides constant-flow inflation and tidal volume delivery independent of respiratory parameter changes. The inclusion of end-inspiratory and end-expiratory pauses simplifies the measurement of airway resistance and compliance and allows the detection of dynamic hyperinflation (auto-positive end-expiratory pressure). After bench testing, we performed intravenous methacholine challenge on two strains of mice (A/J and C57bl/bj) known to differ in their responses by using the new ventilator. Dynamic hyperinflation and a decrease in compliance developed during methacholine challenge whenever respiratory rates of 60-120 breaths/min were employed. In contrast, if dynamic hyperinflation was prevented by lengthening expiratory time, (respiratory rate = 20 breaths/min), static compliance remained constant. More importantly, the coefficient of variation of the results decreased when lung volume shifts were prevented. In conclusion, airway challenge studies have greater precision when dynamic hyperinflation is prevented.

Nasal nitric oxide is not altered by topical anesthesia.

This prospective study was undertaken to determine whether topical nasal anesthetic agents affect nasal nitric oxide (NO) output in healthy adults. Seven volunteers (aged: 29-56 (40.6 +/- 10.7) years, six male), were recruited. A topical anesthetic (4% lidocaine or 0.5% tetracaine) was sprayed into the subject's right nostril while the left nostril served as a control. Unilateral nasal NO and nasal volume were measured before administration of the anesthetic and at 15 and 30 minutes after the administration. The mean (+/- SD) unilateral nasal NO output was 307 +/- 45.9 nL/minute from the right nostril (exposure side) before the topical application of lidocaine. At 30 minutes after topical application (n = 6), it was 295.5 +/- 41.5 in the right nostril and 297.5 +/- 39.8 in the left (control side). In the tetracaine group (n = 7), the mean (+/- SD) unilateral nasal NO output was 302 +/- 53.3 before the administration and 307 +/- 39.7 at 30 minutes after the administration in the right nostril. The mean NO output in the left nostril at 30 minutes after the administration was 297.7 +/- 40.75. In neither group was there any significant difference in nasal NO output between either the pre- and postlocal anesthetic application on the exposure side (Group 1, P = 0.76; group 2, P = 0.41) or the two nostrils after topical anesthesia application (group 1, P = 0.83; group 2, P = 0.62). Topical anesthesia with either lidocaine or tetracaine does not alter nasal NO output. NO measurement should not be affected in circumstances that require topical anesthesia of the nasal cavity.

Airway nitric oxide diffusion in asthma: Role in pulmonary function and bronchial responsiveness.

If the nitric oxide (NO) diffusing capacity of the airways (DNO) is the quantity of NO diffusing per unit time into exhaled gas (q) divided by the difference between the concentration of NO in the airway wall (Cw) and lumen, then DNO and C(w) can be estimated from the relationship between exhaled NO concentration and expiratory flow. In 10 normal subjects and 25 asthmatic patients before and after treatment with inhaled beclomethasone, DNO averaged 6.8 +/- 1.2, 25.5 +/- 3.8, and 22.3 +/- 2.7 nl/s/ppb x 10(-3), respectively; C(w) averaged 149 +/- 31.9, 255.3 +/- 46.4, and 108.3 +/- 14.3 ppb, respectively; and DNOC(w) (the maximal from diffusion) averaged 1,020 +/- 157.5, 6,512 +/- 866, and 2,416 +/- 208.5 nl/s x 10(-3), respectively. DNO and DNOC(w) in the asthmatic subjects before and after steroids were greater than in normal subjects (p < 0.0001), but C(w) was not different. Within asthmatic subjects, steroids caused C(w) and DNOC(w) to fall (p < 0.0001), but DNO was unchanged. DNOC(w) after steroids, presumably reflecting maximal diffusion of constitutive NO, was positively correlated with methacholine PC(20) and FEV(1)/FVC before or after steroids. The increased DNO measured in asthmatic patients may reflect upregulation of nonadrenergic, noncholinergic, NO-producing nerves in airways in compensation for decreased sensitivity of airway smooth muscle to the relaxant effects of endogenous NO.

Hypoxia depresses nitric oxide output in the human nasal airways.

OBJECTIVES: The role of oxygen in the nasal air on nasal nitric oxide (NO) output was studied in 13 adult volunteers. METHODS: Nasal NO was measured while air containing oxygen (0%-100% in nitrogen) was aspirated through the nasal airway before and after the topical application of xylometazoline. RESULTS: The mean nasal NO output of the untreated nose was 507.8 +/- 161.9 nL/min (mean +/- SD) when 21% oxygen was aspirated through the nasal cavities in series and remained unaltered by 100% O2 (P = .79). Below 10% oxygen the reduction in nasal NO output correlated positively and significantly with the decrease in oxygen concentration (r2 = 0.14). NO output was 245.2 +/- 153.4 nL/min at 0% oxygen, a significant decline from 21% oxygen (P < .0001). Nasal vasoconstriction induced by xylometazoline and alterations in the blood oxygen content by a maximal breath-holding or breathing 100% oxygen did not alter nasal NO in hypoxia (P = .41). CONCLUSIONS: Nasal NO output is markedly depressed in hypoxia and is oxygen dependent at concentrations of less than 10%. Approximately 50% of nasally generated NO is produced from oxygen in nasal air or regulated by it.

Lung function 4 years after lung volume reduction surgery for emphysema.

STUDY OBJECTIVES: Current data for patients > 2 years after lung volume reduction surgery (LVRS) for emphysema is limited. This prospective study evaluates pre-LVRS baseline data and provides long-term results in 26 patients. INTERVENTION: Bilateral targeted upper lobe stapled LVRS using video thoracoscopy was performed in 26 symptomatic patients (18 men) aged 67 +/- 6 years (mean +/- SD) with severe and heterogenous distribution of emphysema on lung CT. Lung function studies were measured before and up to 4 years after LVRS unless death intervened. RESULTS: No patients were lost to follow-up. Baseline FEV(1) was 0.7 +/- 0.2 L, 29 +/- 10% predicted; FVC, 2.1 +/- 0.6 L, 58 +/- 14% predicted (mean +/- SD); maximum oxygen consumption, 5.7 +/- 3.8 mL/min/kg (normal, > 18 mL/min/kg); dyspneic class > or = 3 (able to walk < or = 100 yards) and oxygen dependence part- or full-time in 18 patients. Following LVRS, mortality due to respiratory failure at 1, 2, 3, and 4 years was 4%, 19%, 31%, and 46%, respectively. At 1, 2, 3, and 4 years after LVRS, an increase above baseline for FEV(1) > 200 mL and/or FVC > 400 mL was noted in 73%, 46%, 35%, and 27% of patients, respectively; a decrease in dyspnea grade > or = 1 in 88%, 69%, 46%, and 27% of patients, respectively; and elimination of oxygen dependence in 78%, 50%, 33%, and 22% of patients, respectively. The mechanism for expiratory airflow improvement was accounted for by the increase in both lung elastic recoil and small airway intraluminal caliber and reduction in hyperinflation. Only FVC and vital capacity (VC) of all preoperative lung function studies could identify the 9 patients with significant physiologic improvement at > 3 years after LVRS, respectively, from 10 patients who responded < or = 2 years and died within 4 years (p < 0.01). CONCLUSIONS: Bilateral LVRS provides clinical and physiologic improvement for > 3 years in 9 of 26 patients with emphysema primarily due to both increased lung elastic recoil and small airway caliber and decreased hyperinflation. The 9 patients had VC and FVC greater at baseline (p < 0.01) when compared to 10 short-term responders who died < 4 years after LVRS.

Lung function after bilateral lower lobe lung volume reduction surgery for alpha1-antitrypsin emphysema.

This study explores the mechanism(s) of airflow limitation following lung volume reduction surgery (LVRS) in patients with emphysema due to homozygous alpha1-antitrypsin (AT) deficiency. Bilateral targeted lower lobe stapled LVRS using video thoracoscopy was performed in six patients (five males) aged 61+/-9 yrs (mean+/-SD) with alpha1-AT emphysema. Two patients received only a 6-month follow-up. However, four patients, at 22, 24, 27 and 36 months post-LVRS, noted relief from dyspnoea and increased walk tolerance. At 27+/-6 months (mean+/-SD) post-LVRS, their forced expiratory volume in one second improved only from 30+/-2% of the predicted value (mean+/-SEM) before surgery to 33+/-1% pred after surgery. Yet, total lung capacity (TLC) decreased from 151+/-13 to 127+/-10% pred; diffusing capacity increased from 35+/-9 to 59+/-9% pred; and vital capacity increased from 68+/-10 to 88+/-5% pred. In three patients, static lung elastic recoil at TLC increased from 1.1+/-0.15 to 1.2+/-0.10 kPa. Using flow/pressure curves, the mechanism for expiratory airflow limitation pre-LVRS and the improvement noted post-LVRS could be primarily accounted for by the initial loss and subsequent increase in lung elastic recoil. Bilateral lung volume reduction surgery provides modest physiologic improvement for 2-3 yrs in patients with alpha1-antitrypsin emphysema due to increases in lung elastic recoil.

Acoustic rhinometry: a study of transient and continuous noise techniques with nasal models.

The objective of this study is to compare the properties of two of the most frequently used acoustic rhinometers: the EcoVision (Hood Laboratories, USA) using the transient technique, and the Rhin2100 (RhinoMetrics, Denmark) using the continuous wide-band technique. In the wide-band rhinometer (Rhin2100), the transient analog signals of traditional rhinometers (EcoVision), are replaced by a digitally produced continuous wide-band noise signal. Tubular models and a plastic model produced by stereolithography (SLA), representing the true replicate of the nasal anatomy, were used to compare the accuracy of the two rhinometers. The effect of increasing angling (0-50 degrees) between the sound wave tube and the cavity was evaluated in a tubular model. The curves obtained with the two rhinometers showed close similarity, and the acoustically derived volumes correlated well with the volumes of tubular (% error < 4%) as well as the complex nasal model (% error < 10.5%). Both rhinometers underestimated the minimum cross-sectional area (MCA) of the complex nasal model (mean % error complex model: Rhin2100 = -7.6%, EcoVision = -13%). The effect of increasing the angle between the nose adapter and the tubular models was small for both rhinometers (CV < 3% for MCA and CV < 1% for volumes). The similar, and in general, high accuracy of the two rhinometers evaluated, particularly in the complicated geometry of the SLA model, is an indication of the reliability of both. The small effect of changing the angle between the nose adapter and the models was unexpected and very encouraging. Nevertheless, some minor differences in performance and capabilities of the two rhinometers might influence interpretation and comparison of results. Further comparisons in a clinical setting are under current investigation.

Does nasal nitric oxide come from the sinuses?

OBJECTIVE: The purpose of this study was to assess nitric oxide (NO) output by the nose and sinuses. METHOD: In one volunteer, the osteomeatal complex and sphenoethmoidal recess were occluded to isolate the nose from the sinuses. The antrum and frontal sinus were each punctured by two catheters and irrigated with air at constant flow. Nitric oxide output and its rate of accumulation in the absence of air flow were measured in each sinus and in the adjacent nasal cavity. RESULTS: Prior to ostial occlusion, NO output in the nose was 96 nL/min. It decreased by 12% after blockage of all of the ostia. In the isolated sinuses, it was 190 nL/min (antrum) and 68 nL/min (frontal). After 5 minutes stagnation; NO concentration [NO] rose in the occluded sinuses to 24,700 nL/L in the antrum and 22,300 nL/L in the frontal sinus. In the nose, it increased to 29,000 nL/L. When the period of stagnation was prolonged in the frontal sinus, the [NO] reached a plateau. NO output and accumulation were not altered in the nose or either sinus by opening their ostia. In the antrum and frontal sinus, lidocaine reduced NO output and the rate of NO accumulation, but not in the nose. CONCLUSIONS: In this volunteer, 88% of nasal NO was derived from the nose itself. Nitric oxide exchange between the frontal sinus, antrum, and nose was negligible. In the absence of air flow, [NO] rose to a plateau in the nose and frontal sinus. Lidocaine inhibited NO output in the sinuses but not the nose.

Aerodynamic influences on nasal nitric oxide output measurements.

Nitric oxide (NO) concentration in aspirated nasal air is flow-dependent. Nasal NO outputs calculated from steady-state plateaux at flows < 1 l/min are substantially smaller than those at flows > 2 l/min. This study aimed to determine the differences in NO output as calculated from the NO concentration plateaux in aspirated nasal air, resulting from different aspiration flows. Nasal NO was determined by chemiluminescent analysis of air obtained from the nasal passages in series during velopharyngeal closure in 8 healthy adults (flows: 0.2-3.7 l/min) and 5 with symptomatic allergic rhinitis (flows: 0.2-3.7 l/min). Mean NO output in the healthy subjects was stable at approximately 315 nl/l/min at flows of 0.2-0.7 l/min, and increased to a second steady output level of approximately 400 nl/l/min (+28%, p < 0.0001) at more physiological flow rates of 2.7 l/min and higher. The symptomatic subjects had substantially higher NO output at all flows (p < 0.001) (709.3 nl/min at 3.7 l/min) than the non-allergic subjects. The flow dependency of the nasal NO output may be explained by failure at low flows for the air stream to penetrate the peripheral parts of the complex nasal passages, and by the presence of a laminar flow regime in which a marginal lamina would tend to insulate the main stream from the mucosa. Thus, previously reported NO outputs obtained at low flows may underestimate nasal NO output compared to output at higher and more physiological transnasal airflow rates, thus affecting interpretation of results.

Aspiration flow optimized for nasal nitric oxide measurement.

The aim of the present study was to evaluate some of the factors which may influence the reliability of nasal NO measurements, and to optimize methods suitable for children and adults. Nasal nitric oxide (NO) output was determined by chemiluminescent analysis of aspirated samples in 16 adults and 6 children. With the velopharyngeal aperture closed, stable NO levels were obtained at flows ranging form 0.9 to 6.2 L/min. NO output averaged 401.0 +/- 145.4 nL/min./M2 in 6 children, 338.2 +/- 92.3 in 7 adult females and 268.6 +/- 70.2 in 9 adult males. Nasal NO output was independent of flow provided a stable plateau of NO value was reached. In this study, the optimal range of flows was 3.2-5.2 L/min. in adults and 2.2-3.2 L/min. in children. This enables selection of the most favorable flow to be chosen for individual subjects and situations.

Nasal nitric oxide: a comparison of measurement techniques.

Nasal nitric oxide measurement may be a surrogate marker of upper airway inflammation. There is, however, no standardized measurement technique; and this led us to examine measurement techniques for acceptability and reproducibility. In five subjects we examined the flow dependence of nasal NO. In 13 healthy volunteers, nasal NO was measured on-line by five methods: 1) Tidal nasal and oral breathing: NO sampling during exclusive nasal followed by exclusive oral tidal breathing; 2) Fixed flow exhalation: NO sampling during exclusive nasal followed by exclusive oral exhalation at 100 mL/second from total lung capacity; 3) Nasal-oral aspiration: air aspirated from the mouth via both nares at 100 mL/second with glottis closure; 4) Aspiration from one nares: air aspirated from one nares at 3.3 mL/second using nitric oxide analyzer sample line with velum closure; 5) Nasal Insufflation: NO sampled at one nares as air insufflated into the other nares at a flow of 100 mL/second with velum closure. Acceptability of all methods was assessed by subjects and technicians. Nasal NO concentration showed a significant inverse correlation with transnasal flow rate. All methods showed excellent reproducibility as assessed by the intraclass correlation coefficient except tidal breathing, which showed highly variable breath-to-breath NO levels, although mean breath values were reproducible. Mean nasal NO concentrations with methods 1, 2, 3, 4, and 5 were 32.1, 50.2, 62.8, 1381, and 60.0 ppb, respectively. Velum closure was not always achieved in methods 4 and 5, whereas methods 1 and 2 required separate nasal and oral procedures. Method 5 had reduced acceptability. NO concentrations were similar with methods that used the same airflow (2, 3, and 5). Nasal NO can be sampled in different ways with excellent reproducibility. In view of the flow dependence of nasal NO, it is vital to use a constant flow rate, and lower airway NO contribution must be excluded or subtracted. The fixed flow exhalation appears to be the preferred method as it is highly reproducible and acceptable.

Nasal nitric oxide is independent of nasal cavity volume.

This study was performed to evaluate the relationship between nasal nitric oxide (NO) and changes in nasal cavity volume resulting from the topical application of xylometazoline and saline and between upright and supine posture. Nasal NO was measured using a fixed high flow technique that avoids contamination with lower airways NO. In nine healthy subjects nasal NO concentration was measured by a rapid response chemiluminescent analyzer. A tapered tube was inserted in one nostril, into which room air was insufflated to produce a constant flow of 100 mL/second; another tube was inserted into the opposite nostril for NO sampling (air exit side). Subjects were instructed to keep the vellum closed while NO was sampled through a sideport connected to the analyzer. Nasal cavity volume was measured by acoustic rhinometry from a segment of the acoustic pathway, 2 to 5 cm from the nostril. Nasal cavity volume and NO measurements were made at baseline, 15 minutes, and 60 minutes after intervention (administration of saline 0.9%, xylometazoline or posture changes on 3 consecutive days). Xylometazoline produced a significant increase in nasal cavity volume, together with a significant reduction in NO level at 15 and 60 minutes after intervention. In addition, the change from seated to supine position decreased the total nasal volume significantly, but without changes in nasal NO. No correlation was found between the magnitudes of changes in nasal NO and the changes in nasal volume. Topical application of xylomethazoline resulted in increased nasal cavity volume and reduced NO output. In contrast to previous published reports, a technique using high flow rate insufflation demonstrated an abscence of correlation between the magnitudes of changes in nasal NO and nasal cavity volume brought about by decongestant, saline, or posture.

Exhaled nitric oxide as a noninvasive assessment of chronic cough.

Exhaled nitric oxide (ENO) has been suggested as a marker of airway inflammation. This study aimed to evaluate the role of ENO in the investigation of chronic cough. We measured ENO in 38 adult patients reporting chronic cough, in 23 healthy control subjects, and in 44 asthmatics. In addition to the regular investigation, ENO was measured by a chemiluminescent analyzer using the restricted breath technique. In the chronic cough group, 30 were considered as nonasthmatic, whereas asthma was diagnosed in eight by a positive methacholine challenge. ENO values were significantly higher in patients with chronic cough attributable to asthma as compared with those with chronic cough not attributable to asthma and to healthy volunteers (75.0 ppb; 16.7 ppb; and 28.3 ppb, respectively). The sensitivity and specificity of ENO for detecting asthma, using 30 ppb as the ENO cutoff point, were 75 and 87%, respectively. The positive and negative predictive values were 60 and 93%, and the positive and negative likelihood ratios were 5.8 and 0.3, respectively. We conclude that ENO may have a role in the evaluation of chronic cough. In this group of patients, low ENO suggested little likelihood of asthma. The patients with chronic cough not attributable to asthma showed a low ENO value as compared with healthy volunteers and asthmatics.