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Relationship between exhaled carbon monoxide and airway hyperresponsiveness in asthmatic patients.

The study objectives were to analyze the changes in exhaled carbon monoxide (COex) induced by histamine provocation challenge in asthmatic patients and to evaluate the relationship between COex and airway sensitivity and reactivity. Levels of COex were measured in 105 nonsmoking mildly asthmatic subjects before and after histamine provocation challenge. Dose-response curves were characterized by their sensitivity (PD20) and reactivity. Dose-response slope (DRS), continuous index of responsiveness (CIR), and bronchial reactivity index (BRI) were determined as reactivity indices. Bronchial challenge was positive for 47 subjects and negative for 58. The COex levels rose significantly after bronchial challenge in the positive response group (4.49 +/- 0.4 vs. 5.74 +/- 0.57 ppm, p = 0.025) and in the negative response group (2.84 +/- 0.25 vs. 4.00 +/- 0.41 ppm, p = 0.000). An inverse relation between basal COex and PD20 was found (r = -0.318, p = 0.030). In all subjects, a proportional direct relationship between COex and DRS (r = 0.214, p = 0.015), CIR (r = 0.401, p = 0.000), and BRI (r = 0.208, p = 0.012) was observed. On stepwise multiple linear regression analysis, COex only significantly correlated with CIR (multiple r2 = 0.174, p = 0.000). In conclusion, exhaled CO determination is a noninvasive inflammatory marker of the respiratory tract, which shows an acceptable association with airway hyperresponsiveness.

Adult↗

L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m.

We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.

Adult↗

Simple versus sophisticated models of breath alcohol exhalation profiles.

For medicolegal purposes, breath alcohol content is typically determined from an end-expiratory sample. Measurements obtained by this method necessarily underestimate the alveolar breath alcohol content, and therefore underestimate the blood alcohol content. We suggest and analyse an improved paradigm which uses the entire time-series of breath alcohol measurements during exhalation, not simply the last recorded value. We present two mathematical models for the exhaling lung, and discuss the implications of each for more accurate and therefore more reliable breath alcohol measurement.

Adult↗

Natural radionuclides contents and radon exhalation rates in building materials used in South Korea.

The natural radionuclide (226Ra, 232Th and 40K) contents of building materials commonly used in South Korea have been determined by a gamma ray spectroscopy system using a high purity germanium detector. The radon exhalation rates and emanation coefficients of building materials have also been studied. The average concentrations of 226Ra, 232Th and 40K in building materials were in the range of 6.47-271 Bq.kg-1, N.D.-89.9 Bq.kg-1 and 16.8-1081 Bq.kg-1, respectively. The average radon exhalation rates and emanation coefficients were in the range of 0.0061-0.2404 Bq.kg-1.h-1 and 2.39-11.5%, respectively.

Construction Materials↗

Validation of a geographic information system for the evaluation of the soil radon exhalation potential in South-Tyrol and Veneto, Italy.

The PERS (soil radon exhalation potential) project was promoted by ANPA (Italian Environmental Protection Agency) together with the Università Cattolica del Sacro Cuore of Rome: the aim was to produce a geographic information system allowing the discovery of regions with different radon exhalation potential starting from some territorial knowledge. Some environmental measurements were carried out within this project in selected areas in South-Tyrol and Veneto. The measurement of radon in springwater and groundwater as well as in soil gas plays a decisive role for the validation of the algorithm for computing the PERS. Along with technical aspects, a possible use of the PERS method by the Regional Environmental Protection Agencies and by other agencies is discussed with the scope of identifying radon prone areas, as stated in the Italian 'Decreto Legislativo' 26 May 2000, n. 241. Moreover the forecasting power of PERS regarding indoor radon concentration is analysed.

Geography↗

Rebreathing of exhaled gases: importance as a mechanism for the causal association between prone sleep and sudden infant death syndrome.

Twenty to 52% of sudden infant death syndrome (SIDS) victims are found dead with their noses and mouths turned into underlying bedding. Several items of bedding have been shown to increase the risk for SIDS in case-control studies or to be associated with many SIDS deaths in case series. These items of bedding are after limit CO2 dispersal more, and cause more rebreathing of exhaled gases than bedding infrequently associated with SIDS. Rebreathing of exhaled gases may explain some prone deaths, and avoiding rebreathing of these gases is one possible mechanism for the reduction in SIDS when infants avoid prone sleep. Results supporting these statements are reviewed and discussed.

Carbon Dioxide↗

A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics.

The inducible isoenzyme of nitric oxide synthase (iNOS) generates nitric oxide (NO) in inflammatory diseases such as asthma. The prodrug L-N6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51) is rapidly converted in vivo to the active metabolite L-N6-(1-iminoethyl)lysine (L-NIL). Initially, we performed in vitro experiments in human primary airway epithelial cells to demonstrate that L-NIL causes inhibition of iNOS. In a randomized double-blind placebo-controlled crossover trial, SC-51 was administered as a single oral dose (20 or 200 mg) in separate cohorts of healthy volunteers (two groups of n=12) and mild asthmatic patients (two groups of n=12). SC-51 (200 mg) reduced exhaled breath NO levels to <2 ppb in both healthy volunteers (P<0.001) and mild asthmatics (P<0.001) within 15 min, representing >90% inhibition of baseline levels of NO in asthmatic patients, with the effects lasting at least 72 h. There were no significant effects on blood pressure, pulse rate, or respiratory function (FEV1). This study demonstrates that an inhibitor of iNOS produces marked inhibition of exhaled breath NO in normal and asthmatic subjects without producing the side effects observed following the systemic administration of non-selective NOS inhibitors, and thus provides support for the potential use of iNOS inhibitors to treat a range of inflammatory clinical disorders.

Administration, Oral↗

Natural radioactivity in and radon exhalation from Finnish building materials.

A total of 369 samples of Finnish building materials were tested for their 226Ra, 232Th and 40K concentrations. The rate of radon exhalation was measured from 19 samples of material and 34 dwellings were tested for their room air ventilation rate and radon concentration. The mean values of 226Ra, 232Th and 40K concentrations in ballast materials for concrete production were 34.2 Bq X kg-1, 39.0 Bq X kg-1 and 964 Bq X kg-1, with standard deviations of 18.7 Bq X kg-1, 19.5 Bq X kg-1 and 265 Bq X kg-1, respectively. The activity concentrations were higher in clay bricks than in concrete, the mean values being 79.8 Bq X kg-1, 61.6 Bq X kg-1 and 986 Bq X kg-1 for 226Ra, 232Th and 40K, respectively. The normalized radon exhalation rates from 15-cm-thick concrete, slag-aggregate concrete and by-product gypsum were 0.38 (Bq X m-2 X h-1)/(Bq X kg-1), 0.15 (Bq X m-2 X h-1)/(Bq X kg-1), and 0.06 (Bq X m-2 X h-1)/(Bq X kg-1), respectively. The ventilation rates in dwellings varied between 0.27 and 1.99 air changes per h, the mean value being 0.60 h-1, and the corresponding steady state radon concentrations in room air varied from 17.0 to 149 Bq X m-3 in blocks of flats made of concrete and from 11.2 to 61.9 Bq X m-3 in blocks of flats made of brick.

Air Pollutants, Radioactive↗

Discussion about surface boundary conditions of radon concentration and surface exhalation rate calculations in indoor concrete slab.

In this paper, the rationality of boundary conditions that assume radon concentration at the surface of a concrete slab to be zero, or radon concentration at an infinite point in air to be zero, are discussed in the calculations of radon concentration and surface exhalation rate from a concrete slab. Expressions to calculate radon concentration and surface exhalation rate in indoor concrete slab are given for both boundary conditions.

Air Pollutants, Radioactive↗

Assessment of radioactivity and radon exhalation rate in Egyptian cement.

The cement industry is considered as one of the basic industries that plays an important role in the national economy of developing countries. Activity concentration of 238U, 232Th, and 40K in local cement types from different Egyptian factories has been measured using a shielded HPGe detector. The average values obtained for 238U, 232Th, and 40K activity concentrations in different types of cement are lower than the corresponding global values reported in UNSCEAR publications. On the basis of the hazard index and the radium equivalent concentration, it can be shown that the natural radioactivity of cement samples is not greater than the values permitted in the established standards in other countries. A solid-state nuclear track detector SSNTD (Cr-39) was used to measure the radon concentration as well as exhalation rate for these samples. The effective radium content and the exhalation rate are found to vary from 12.75 to 38.52 Bq kg(-1) and 61.19 to 181.39 Bq m(-2) d(-1), respectively.

Construction Materials↗

Exhaled nitric oxide as an indicator of severity of asthmatic inflammation.

Traditional assessment of severity of asthma relies on an evaluation of signs and symptoms and pulmonary function tests. These pulmonary function tests, such as peak expiratory flow rates, forced vital capacity, and forced expiratory flow rates, are indirect measures of airway caliber only, and not inflammation. Since asthma is an inflammatory disease, a measure of the degree of inflammation would be helpful in quantitating severity and titrating of anti-inflammatory therapy. A noninvasive method for measuring pulmonary inflammation would therefore be helpful to assist the emergency physician in initial treatment and assist in titration of anti-inflammatory therapy during repeat visits. Exhaled nitric oxide (NO) assays are convenient and practical and may fulfill this role. In this review, we discuss the role of NO in asthmatic inflammation and the role that exhaled NO values may play in the emergency management of asthma.

Asthma↗

Utility of exhaled breath condensates in chronic obstructive pulmonary disease: a critical review.

PURPOSE OF REVIEW: Evaluation of the utility of exhaled breath condensates in chronic obstructive pulmonary disease. RECENT FINDINGS: Exhaled breath condensates have recently been introduced as a simple, noninvasive method of sampling respiratory fluid in inflammatory lung disorders, including chronic obstructive pulmonary disease. Increases in condensate concentrations of at least 12 markers of inflammation have been reported in these disorders. Furthermore, condensate pH appears to be decreased in both chronic obstructive lung disease and bronchial asthma. This has been referred to as acidopnea and could reflect airway acidification by inflammatory cells. Although safer and more convenient than bronchoalveolar lavage, interpretation of condensate data is complicated by uncertainty regarding the source of condensate solutes and by variable dilution of respiratory droplets from condensed water vapor, which represents more than 99.9% of condensate volumes. This dilution can be estimated from the dilution of plasma constituents such as urea or electrolytes. Because the principal buffer in condensate is NH4, much of which is derived from bacterial degradation of urea in the mouth, condensate pH measurements may not provide accurate estimates of airway pH. Nevertheless, acidification of condensate may be indicative of gastroesophageal reflux, which frequently occurs in obstructive lung diseases and may contribute to cough and bronchospasm. SUMMARY: It is too early to tell how useful condensate studies will be to pulmonary investigators and clinicians. Realization of the enormous potential of this approach will require a thorough understanding of the manner in which these solutions are generated and how they should be analyzed.

Acidosis, Respiratory↗

Exhaled markers of inflammation.

Exhaled markers of inflammation allow completely noninvasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis and interstitial lung diseases. Such noninvasive techniques are simple to perform, may be repeated frequently and can be applied in children, including neonates and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, hydrocarbons), and many nonvolatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate.

Biomarkers↗

Exhaled nitric oxide during normoxic and hypoxic exercise in endurance athletes.

AIM: Endogenous nitric oxide (NO) through its relaxing effect on smooth muscle cells may be involved in pulmonary gas exchange as well as in the modulation of the hypoxic pulmonary vasoconstriction. As athletes with exercise-induced hypoxaemia (EIH) present pulmonary gas exchange abnormalities in normoxia that could be even greater in hypoxia, we hypothesized that pulmonary NO may be lower in such athletes with EIH. METHODS: Eleven athletes with EIH [decrease in arterial oxygen blood partial pressure (PaO2) > 12 mmHg] and 9 without EIH (NEIH) exercised at 40%, 60% (10 min) and 90% (5 min) of normoxic maximal power output (Pmax) in normoxia, and at 40% and 60% (10 min) of Pmax in hypoxia (FiO2 = 15%). Exhaled NO concentration during a constant flow exhalation (FENO(0.170)) and arterialized blood gases were measured at every power output. RESULTS: FENO(0.170) decreased from rest to exercise both in normoxia (-27.8 +/- 22.8% at 90% Pmax, P < 0.001) and hypoxia (-23.8 +/- 17.5% at 60% Pmax, P < 0.001). At 90% Pmax in normoxia, EIH athletes showed lower PaO2 (76.7 +/- 5.4 vs. 82.8 +/- 4.4 mmHg, P = 0.013) and greater FENO(0.170) decrement (-37.0 +/- 24.7% vs. -16.6 +/- 14.6%, P = 0.042) than NEIH athletes. During hypoxic exercise, P(a)O(2) and FENO(0.170) decreases were similar in both groups (P > 0.05). CONCLUSION: The present study shows lower pulmonary NO in athletes with gas exchange abnormalities during intense exercise in normoxia, while EIH and NEIH athletes have similar decreases in blood gases and pulmonary NO during hypoxic exercise. Decreased pulmonary NO in such conditions may contribute to ventilation-perfusion inequality and/or increase pulmonary vascular tone in athletes.

Adult↗

Exhaled nitric oxide: relation to sensitization and respiratory symptoms.

BACKGROUND: Conflicting data have been presented as to whether nitric oxide (NO) in exhaled air is merely reflecting atopy rather than airway inflammation. OBJECTIVE: To investigate the relationship between exhaled NO (eNO) and nasal NO (nNO), respiratory symptoms, and atopy, in the context of a cross-sectional study of the respiratory health of bleachery workers. METHODS: Two hundred and forty-six non-smoking bleachery and paper-mill workers answered a questionnaire and were examined by measurements of eNO and nNO and spirometry, outside the pollen season. Blood samples were collected and analysed for specific IgE against common aeroallergens (birch, timothy, cat and house dust mite). Atopy was defined as a positive Phadiatop trade mark test. RESULTS: The atopic and the non-atopic subjects without asthma or rhinitis had similar levels of eNO. Subjects reporting asthma or rhinitis who were also sensitized to perennial allergens had higher levels of eNO, whereas those sensitized to only seasonal allergens had similar eNO levels as non-atopic subjects with asthma or rhinitis. In multiple linear regression models adjusted for nNO, eNO was associated with asthma and sensitization to perennial allergens. CONCLUSION: The results indicate that only atopic subjects who have recently been exposed to the relevant allergen have elevated levels of eNO. Atopic subjects who are not being exposed to a relevant allergen or have never experienced symptoms of asthma or rhinitis show normal eNO. These data indicate that eNO relates to airway inflammation in atopic subjects.

Adult↗

Allergic rhinitis with or without concomitant asthma: difference in perception of dyspnoea and levels of fractional exhaled nitric oxide.

BACKGROUND/AIM: Allergic rhinitis (AR) is a risk factor for developing clinical asthma. Moreover, AR is often associated with bronchial hyper-responsiveness (BHR). The aim of the present study was to investigate whether patients with AR and asthma differed from AR with or without BHR in degree of perception of dyspnoea and airway inflammation, measured as fractionated exhaled nitric oxide (NO). MATERIALS: Twenty-nine patients with seasonal AR (timothy) were investigated with metacholine challenge test. Fourteen healthy non-reactive subjects served as controls. METHODS: (1) Metacholine challenge test, cut-off value forced expiratory volume in 1 s (FEV(1)) PD20 2,000 microg. Slope value for metacholine was calculated as %fall in FEV(1)/mol metacholine. Dyspnoea during challenge was measured with a 10-graded modified Borg score. (2) Measurement of fractional-exhaled nitric oxide (FENO) at flow rate 50 mL/s. RESULTS: Eighteen patients reported AR only, without asthma symptoms, and 12 (67%) were BHR. Eleven subjects had both rhinitis and asthma symptoms. Patients with rhinitis and asthma reported significantly more dyspnoea per percent fall in FEV(1) compared with those with rhinitis and BHR. Moreover, those with rhinitis and asthma had significantly higher NO values compared with those with rhinitis and BHR. CONCLUSION: The difference between rhinitis patients with or without asthma symptoms seems to be mainly a question of perception of dyspnoea. However, FENO measurement indicates that dyspnoea may also be associated with increased inflammatory activity in the peripheral airways.

Adult↗

Exhaled breath condensate levels of eotaxin and macrophage-derived chemokine in stable adult asthma patients.

BACKGROUND: Asthma is associated with esoinophilic airway inflammation and overproduction of T-helper type 2 (Th2) lymphocyte-related cytokines. OBJECTIVE: This study assessed the eosinophil chemoattractant eotaxin and Th2-specific macrophage-derived chemokine (MDC) in the adult asthmatic airway. Eotaxin and MDC levels were determined in exhaled breath condensate (EBC) obtained from adult patients with asthma. METHODS: Fifty-four asthmatics (20 male, mean (SD) age 40 (12) years and percentage predicted forced expiratory volume in 1 s (FEV(1)) 81.7 (20.8)) and 20 age- and sex-matched controls were studied. EBC was collected using EcoScreen by 10 min of tidal breathing with a nose clip. Concentrations of eotaxin and MDC were measured by ELISA. RESULTS: Asthma patients on inhaled corticosteroid (ICS) had a higher median interquartile range (IQR) level of eotaxin than the steroid-naïve asthmatics (18.5 (17.7-20.1) vs. 17.9 (17.0-18.6) pg/mL, P=0.02) and controls (18.5 (17.7-20.1) pg/mL vs 17.4 (16.3-18.0) pg/mL, P=0.001). Eotaxin level in EBC had a significant negative correlation with the FEV(1)/forced vital capacity ratio (r=-0.43, P=0.03) in steroid-naïve asthmatics. EBC MDC level was higher in subjects on ICS than the steroid naïve asthmatics (120 (118-125) vs. 117 (116-119) pg/mL, P=0.01) and the controls (120 (118-125) vs. 117 (116-120) pg/mL, P=0.02). CONCLUSIONS: Eotaxin and MDC could be measured in EBC of adults with asthma. EBC eotaxin and MDC levels were higher in asthmatics on ICS than the steroid-naïve asthmatics or controls. Exhaled chemokines may be potential non-invasive markers for assessing airway inflammation in asthmatics.

Administration, Inhalation↗

Nicotinamide does not influence cytokines or exhaled NO in human experimental endotoxaemia.

This study examined the hypothesis that nicotinamide could attenuate endotoxin-induced inflammatory responses in humans as indicated by levels of cytokines and nitric oxide. Ten healthy male volunteers participated in a randomised, double-blind, cross-over design with regard to the effects of nicotinamide. The volunteers received orally 4 g nicotinamide or placebo at 14 h and at 2 h preceding the experiment (total dose of 8 g). Endotoxin (E. coli, 2 ng/kg), was administered intravenously. Blood samples and haemodynamic data were collected prior to and up to 6 h after the endotoxin infusion. Orally exhaled NO was measured hourly. Following endotoxin, body temperature increased from baseline 36.3 +/- 0.09 degrees C to a maximum of 38.0 +/- 0.1 degrees C for all (mean +/- SEM, P < 0.001) and heart rate increased from 59 +/- 1.9 to 87.0 +/- 2.6 beats/min after 3 h (mean +/- SEM, P < 0.001). Endotoxin challenge also markedly elevated the TNF-alpha, IL-6, IL-8 and IL-10 concentrations (P < 0.001 versus baseline for all) during the study period. Orally exhaled NO also increased (P < 0.01) compared to baseline. Nicotinamide treatment did not influence the patterns of cytokine and NO response to endotoxin. In conclusion, there was no effect on the inflammatory parameters by oral nicotinamide at a dose of 8 g, limiting the potential use of this agent for anti-inflammatory purpose in man.

Adult↗