Exhaled and nasal nitric oxide in laryngectomized patients.

BACKGROUND: Nitric oxide (NO) shows differing concentrations in lower and upper airways. Patients after total laryngectomy are the only individuals, in whom a complete separation of upper and lower airways is guaranteed. Thus the objective of our study was to assess exhaled and nasal NO in these patients. METHODS: Exhaled bronchial NO (FENO) and nasal nitric oxide (nNO) were measured in patients after total laryngectomy (n = 14) and healthy controls (n = 24). To assess lung function we additionally performed spirometry. Co-factors possibly influencing NO, such as smoking, infections, and atopy were excluded. RESULTS: There was a markedly (p < 0.001) lower FENO in patients after total laryngectomy (median (range): 4 (1-22) ppb) compared to healthy controls 21 (9-41) ppb). In contrast, nNO was comparable between groups (1368 versus 1380 in controls) but showed higher variability in subjects after laryngectomy. CONCLUSIONS: Our data suggest that either bronchial NO production in patients who underwent laryngectomy is very low, possibly due to alterations of the mucosa or oxidant production/inflammation, or that substantial contributions to FENO arise from the larynx, pharynx and mouth, raising FENO despite velum closure. The data fit to those indicating a substantial contribution to FENO by the mouth in healthy subjects. The broader range of nNO values found in subjects after laryngectomy may indicate chronic alteration or oligo-symptomatic inflammation of nasal mucosa, as frequently found after total laryngectomy.

Lung diffusing capacity for nitric oxide and carbon monoxide in relation to morphological changes as assessed by computed tomography in patients with cystic fibrosis.

BACKGROUND: Due to large-scale destruction, changes in membrane diffusion (Dm) may occur in cystic fibrosis (CF), in correspondence to alterations observed by computed tomography (CT). Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO), as opposed to the conventional diffusing capacity for carbon monoxide (DLCO). We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. METHODS: Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean +/- SD age 35 +/- 9 y, FEV1 66 +/- 28%pred). Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS) with z-scores of functional measures were computed. RESULTS: CT scores correlated best with DLNO (rS = -0.83; p < 0.001). Scores were also related to the volume-specific NO transfer coefficient (KNO; rS = -0.63; p < 0.01) and to DLCO (rS = -0.79; p < 0.001) but not KCO. Z-scores for DLNO were significantly lower than for DLCO (p < 0.001). Correlations with spirometric (e.g., FEV1, IVC) or bodyplethysmographic (e.g., SRaw, RV/TLC) indices were weaker than for DLNO or DLCO but most of them were also significant (p < 0.05 each). CONCLUSION: In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF.

Exhaled nitric oxide: independent effects of atopy, smoking, respiratory tract infection, gender and height.

Measurement of exhaled nitric oxide is widely used in respiratory research and clinical practice, especially in patients with asthma. However, interpretation is often difficult, due to common interfering factors, and little is known about interactions between factors. We assessed the influences and interactions of factors such as smoking, respiratory tract infections and respiratory allergy concerning exhaled nitric oxide values, with the aim to derive a scheme for adjustment. We studied 897 subjects (514 females, 383 males; mean age+/-standard deviation 34.5+/-13.0 years) with and without respiratory allergy (allergic rhinitis and/or asthma), smoking and respiratory tract infection. Logarithmic nitric oxide levels were described by an additive model comprising respiratory allergy, smoking, respiratory tract infection, gender and height (p0.001 each), without significant interaction terms. Geometric mean was 17.5ppb in a healthy female non smoker of height 170cm, whereby respiratory allergy corresponded to a change by factor 1.50, smoking 0.63, infection 1.24, male gender 1.17, and each 10cm increase (decrease) in height to 1.11 (0.90). Factors were virtually identical when excluding asthma and using the category allergic rhinitis instead of respiratory allergy (n=863). Within each category formed by combinations of these different predictors, the range of residual variation was approximately constant. We conclude that the factors influencing exhaled nitric oxide, which we analyzed, act independently of each other. Thus, circumstances such as smoking and respiratory tract infection do not appear to affect the usefulness of exhaled nitric oxide, provided that appropriate factors for adjustment are applied.

Lung diffusing capacity for nitric oxide and carbon monoxide: dependence on breath-hold time.

BACKGROUND: The combined measurement of diffusing capacity of the lung for nitric oxide (Dlno) and diffusing capacity of the lung for carbon monoxide (Dlco) is a simple, noninvasive tool, but methodologic factors might influence results and reproducibility. We thus quantified the influence of breath-hold time on Dlco and Dlno in subjects with or without airway disease. METHODS: Simultaneous single-breath measurements of Dlco and Dlno were performed in 10 patients with cystic fibrosis (CF) [mean +/- SD age, 33 +/- 9 years; FEV(1), 69 +/- 28% of predicted] and 10 healthy subjects (age, 31 +/- 9 years; FEV(1), 108 +/- 8% of predicted), using the Masterscreen PFT (Viasys/Jaeger; Höchberg, Germany), with 45 ppm of inspired nitric oxide (NO), and breath-hold times of 4 s, 6 s, 8 s, and 10 s. The last two of three consecutive measurements were used for analysis. RESULTS: In healthy subjects but not patients with CF, Dlno, and Dlco differed significantly (p < 0.05 each) between breath-hold times. Differences primarily occurred at 4 s and 10 s, while at 6 s and 8 s alveolar volume (VA), Dlno, Dlco, and Dlno/Dlco were similar. Variability of consecutive measurements (either three or the last two measurements) did not depend on breath-hold time. At 8 s, mean variabilities of Dlno and Dlco in healthy subjects were 4.9% and 2.5%, respectively, and 4.2% and 3.2% at 6 s. At 8 s, mean variabilities of Dlno and Dlco in CF patients were 4.4% and 1.9%, and 7.4% and 3.3% at 6 s. CONCLUSIONS: Single-breath determinations of dlno and dlco showed no difference between breath-hold times of 6 s and 8 s in subjects with or without airway obstruction, and reproducibility was acceptable. Standardization of breath-hold time for Dlno measurements seems important for clinical and research comparisons.

The physical and biological doses of methacholine are different for Mefar MB3 and Jaeger APS sidestream nebulizers.

BACKGROUND: Within a study on respiratory symptoms in rural areas, we used the European Community Respiratory Health Survey methacholine challenge protocol. For quicker and more reliable handling, we had to change the nebulizer in the bronchial challenge system from Mefar model MB3 (Bovezzo, Italy) to Jaeger APS Sidestream (similar to Mefar; Würzburg, Germany). Therefore, we compared the physical properties of the two systems, adapted the challenge protocol, and compared the results of both systems in subjects with and without airway hyperresponsiveness to methacholine. METHOD: The physical properties of both systems were characterized by the residual method indicating a similar particle size distribution and an average output of 6 muL/s for Mefar MB3 and 1.25 muL/s for APS Sidestream. In the comparison study, 34 subjects were included. Airway responsiveness was quantified by provocative dose of methacholine causing a 20% fall in FEV(1). RESULTS: A significant difference was found between the two challenge systems (p =0.004, McNemar test). Nine subjects reached a 20% drop in FEV(1) with the APS Sidestream only. The FEV(1) dropped by > 20% using either system in eight subjects. In 17 subjects, none of the two systems caused a 20% decrease in FEV(1). CONCLUSION: Even if the physical dose is determined with elaborate methods, the biological dose may vary between two nebulizer systems, causing incomparable outcomes for subjects tested with different systems.