The measurement of exhaled carbon monoxide in healthy smokers and non-smokers

The measurement of exhaled carbon monoxide (CO) level may provide an immediate, non-invasive method of assessing smoking status. The aims of this study were to use a portable CO monitor to compare the exhaled CO levels in established smokers and non-smokers. The exhaled CO levels were measured in 322 subjects (243 healthy smokers, 55 healthy non-smokers, 24 passive smokers) who applied to healthy stand during the spring student activity of Firat University in Elazi?. Exhaled CO concentration was measured using the EC50 Smokerlyser. The mean exhaled CO level was 17.13+/-8.50 parts per million (ppm) for healthy smokers and 3.61+/-2.15 ppm for healthy non-smokers, and 5.20+/-3.38 ppm for passive smokers. There were significant positive correlation between CO levels and daily cigarette consumption, and CO levels and duration of smoking in healthy smokers (r=+0.550, P<0.001, r=+0.265, P<0.001, respectively. Spearman's test). When smokers and non-smokers were looked at as a whole, a cutoff of 6.5 ppm had a sensitivity of 90% and specificity of 83%. In conclusion, exhaled CO level provides an easy, an immediate way of assessing a subject's smoking status.     

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.     

Factors influencing the levels of exhaled carbon monoxide in asthmatic children

Objective: Bronchial asthma is characterised by chronic airway inflammation commonly associated with increased oxidative stress. Exhaled carbon monoxide (eCO) levels could act as markers of both oxidative stress and allergic inflammation. We aimed to study eCO levels in asthmatics and detect the possible factors influencing them. Methods: We studied 241 asthmatic children and 75 healthy children. The differences in eCO levels among various asthmatic phenotypes and the correlations between eCO and other measured parameters (spirometric indices, Asthma Control Test score, exhaled nitric oxide, total IgE, blood eosinophils and marker of oxidative damage of proteins) were analysed. Results: Levels of eCO widely differed according to the selected characteristics of asthma. Asthmatics showed higher eCO concentrations than controls (1.44?±?0.12?ppm vs. 0.91?±?0.11?ppm, p?p?Conclusions: In a population of asthmatic children, eCO levels could be considered as a marker of both allergic inflammation and oxidative stress in the airways. Concomitant AR and asthma control were the most important factors affecting the levels of eCO in asthmatic children. However, our results do not support the use of routine eCO in the clinical practice.     

The management of life-threatening airflow obstruction

Summary Patients with status asthmaticus commonly develop progressive airflow obstruction over hours to days as a result of airway wall inflammation, bronchospasm and intraluminal mucus. In sudden asphyxic asthma, airflow obstruction results primarily from smooth muscle mediated bronchospasm. Airflow obstruction causes ventilation-perfusion inequality, lung hyperinflation, and increased work of breathing. Severe cases are characterized by an inability to speak, diaphoresis, altered mental status, poor air movement, widened pulsus paradoxus, accessory muscle use, and low peak expiratory flow rate. Lack of early response to bronchodilator therapy, a rising partial pressure of carbon dioxide, and need for assisted ventilation are additional markers of severe disease. First line treatment consists of oxygen, beta agonists, and corticosteroids. In mechanically ventilated patients, bronchodilators must be given in higher dosages to achieve a physiologic effect. Agents of debated efficacy include theophylline, anticholinergics, and magnesium sulfate. Heliox and noninvasive positive pressure ventilation are promising adjuncts to the treatment of nonintubated patients. In patients requiring intubation and mechanical ventilation, a ventilatory strategy should be used that avoids excessive lung hyperinflation by prolonging expiratory time. In many cases, this strategy requires acceptance of hypercapnea and high peak airway pressures. Patients should be aggressively sedated to decrease the need for muscle paralysis and the risk of post paralytic myopathy. Indirect evidence suggests that the current approach to mechanical ventilation in acute severe asthma decreases morbidity and mortality; however, the key to the management of this disease (which in many cases represents a failure of outpatient management) is patient education and disease prevention. Received: 25 October 1996 Accepted: 13 November 1996     

The association between airflow obstruction and radiologic change by tuberculosis

Introduction

Cigarette smoking is the most commonly encountered risk factor for chronic obstructive pulmonary disease (COPD). However, it is not the only one and there is consistent evidence from epidemiologic studies that nonsmokers may develop chronic airflow limitation. A history of tuberculosis has recently been found to be associated with airflow obstruction in adults older than 40 years. The aim of this study was to evaluate the association between the radiologic changes by tuberculosis and airflow obstruction in a population based sample.

Methods

A nationwide COPD prevalence survey was conducted. We compared the prevalence of airflow obstruction according to the presence of the radiologic change by the tuberculosis.

Results

We analyzed 1,384 subjects who participated in the nationwide Korean COPD survey. All subjects were older than 40 years and took the spirometry and simple chest radiography. We defined the airflow obstruction as FEV₁/FVC <0.7. A total of 149 (10.8%) subjects showed airflow obstruction. A total of 167 (12.1%) subjects showed radiologic change by tuberculosis. Among these 167 subjects, 44 (26.3%) had airflow obstruction. For the subjects without radiologic change by tuberculosis, the prevalence of airflow obstruction was only 8.6%. The unadjusted odds ratio for airflow obstruction according to the radiologic change was 3.788 (95% CI: 2.544-5.642).

Conclusions

The radiologic change by tuberculosis was associated with airflow obstruction.     

Within-breath changes of airway calibre in patients with airflow obstruction by continuous measurement of respiratory impedance

We bench-tested a commercially available instrument for measuring respiratory impedance (Siregnost FD5: Siemens) and found that resistance (R) and phase changes were accurately recorded in models. In a single human subject, total respiratory resistance (R(l)) was closely comparable to resistance measured by the Mead-Whittenberger technique. The derived continuous variable (R(os)) was similar to R at less than 4 cmH2O . litres-1 . sec, but underestimated R at higher values. Ros was highly correlated with airways resistance by body plethysmography (R(aw)), but with a low slope and high intercept (R(os) = 1.38 + 0.59 R(aw): r = 0.89). Because of turbulence, both in model larynxes and in normal subjects, R(os) tends to rise with increases in flow in either direction. R(os) also tends to fall as lung volume rises, and vice versa, reflecting cyclic changes in airway calibre. We devised indices of expiratory narrowing of airways from the maximum flow-volume loop, and the plethysmographic alveolar pressure-flow loop, and compared them with the slope of the relation between R(os) and lung volume during tidal breathing, in nine normal subjects and 16 patients with airflow obstruction. Twelve of the 16 patients, all with abnormal flow-volume loops, had high R(os)-volume slopes, demonstrating excessive expiratory narrowing even during tidal breathing. We found no patients with normal inspiratory R(os) together with an abnormal R(os)-volume slope. Thus unstressed inspiratory calibre was never dissociated from airways narrowing on expiration.     

Exhaled monoxides as a pulmonary function test: use of exhaled nitric oxide and carbon monoxide.

Although there has been tremendous improvement in the technologic ability to measure exhaled gases and monitor biologic processes in the lung, it has not yet found a clinical role outside the research laboratory. Common themes seem to be significant overlap in the amount of exhaled gases in clinically distinct populations, confounding variables such as infection, smoking, and environmental exposure, and lack of consistent change with disease management. If these tests are ever to be used by the general pulmonologist, consistent links between the measurements and the response to disease modification will need to be demonstrated at the very least and, ideally, the clinician would like to see improved outcomes when these noninvasive tests are employed regularly.     

Changes in exhaled carbon monoxide and nitric oxide levels following allergen challenge in patients with asthma.

Carbon monoxide is a product of haem degradation by haem oxygenase (HO), activated by inflammatory cytokines and oxidants. This study examined whether allergen challenge can increase exhaled CO levels, as a reflection of HO activation. Exhaled CO and nitric oxide, an expired gas also thought to reflect cytokine-induced airway inflammation, were measured in 15 atopic steroid-naive nonsmoking patients with asthma (13 males, aged 30+/-2 yrs) before and for up to 20 h after allergen challenge. Baseline CO (4.4+/-0.3 parts per million (ppm)) and NO (20.6+/-1.2 parts per billion (ppb)) levels were elevated in asthmatic as compared with nonsmoking normal volunteers (n = 37, 2.1+/-0.2 ppm and 7.0+/-0.1 ppb, respectively, p<0.05). In 10 patients with a dual response in the forced expiratory volume in one second (FEV1) there was a maximal increase in exhaled CO at 1 h (343+/-7.1%) and at 6 h (69+/-12%, p<0.01), followed by a maximal fall in FEV1 (28+/-9%, p<0.05) at 9 h, whereas the maximal NO increase was observed at 10 h (50.2+/-11.8%). The maximal increase in exhaled CO in single response patients (n = 5) was 30+/-2% during the early asthmatic reaction and 46.3+/-9.2% between 4 and 10 h, followed by a fall in FEV1 (9+/-3%, p>0.05) at 9 h, whereas exhaled NO was not significantly changed. In five patients exhaled CO was not attenuated by inhalation of increasing concentrations of histamine causing a 20% fall in FEV1 (PC20) or its subsequent relief by beta2-agonists. In conclusion, exhaled carbon monoxide is increased during the early and late asthmatic reactions independently of the change in airway calibre, while exhaled nitric oxide is increased only during the late reaction and follows the increase in carbon monoxide and fall in the forced expiratory volume in one second in time.     

The significance of wheezing in chronic airflow obstruction

Eighty-three patients with chronic airflow obstruction were examined prospectively to determine the relationships among wheezing intensity, severity of obstruction, and response to inhaled isoproterenol. For each patient, expiratory wheezing scores were assigned during deep unforced breathing and during forced vital capacity efforts at spirometry. Unforced wheezing scores were independently correlated with severity of obstruction (r = 0.42) and bronchodilator response (r = 0.46), but these correlations did not permit consistent prediction of either variable for clinical purposes. The highest wheezing scores, however, were uniformly associated with moderate or severe obstruction. Twenty-nine of 48 patients with wheezing but only 3 of 35 patients without wheezing demonstrated 15% or greater improvement in one-second forced expiratory volume after bronchodilator inhalation (p less than 0.001). Wheezing during forced exhalation was not correlated with either degree of obstruction or bronchodilator response.     

Moderately severe chronic airflow obstruction. Can corticosteroids slow down obstruction?

In a former study in patients with severe chronic airflow obstruction (CAO), (forced expiratory volume in one second (FEV1) ranging from 350-910 ml), we concluded that daily oral corticosteroids might slow down the progression of disease. The results of the present long-term (14-20 yr) study on 139 non-allergic patients with less severe CAO (FEV1 greater than or equal to 1200 ml, FEV1 as a percentage of vital capacity (FEV1%VC) 40-55%) confirm and extend our former observations. Four patterns of the course of FEV1 and inspiratory vital capacity (VC) in time were recognized: 1) linear decrease; 2) no change; 3) initial increase, followed by decrease; 4) initial decrease, followed by increase. Groups 1 and 3 had a higher functional residual capacity as a percentage of total lung capacity (FRC%TLC) as compared to group 2 and 4; the work of breathing was lower in group 2 than in the other three groups. Otherwise the initial 82 parameters, including the degree of reversibility of airflow obstruction and smoking habits were comparable in the four groups. The four patterns of FEV1 showed a strong association with the long-term use of prednisolone. When oral prednisolone was instituted or increased to a dose of at least 10 mg/day continuously, FEV1 either remained constant, decreased more slowly or even increased over many years of follow-up. When the oral dose was diminished to below 10 mg/day, FEV1 decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Basis of guanylate cyclase activation by carbon monoxide.

Kinetics of CO association with guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] and dissociation from carboxy guanylate cyclase have been studied at pH 7.5 by flash photolysis, yielding rate constants at 23 degrees C of 1.2 +/- 0.1 x 10(5) M-1.sec-1 and 28 +/- 2 sec-1, respectively. While the CO combination rate constant is the same as for the T state of hemoglobin, the CO dissociation rate constant is much higher than expected for a six-coordinate carboxyheme protein; yet the absorption spectrum is indicative of a six-coordinate heme. The two observations are reconciled by a reaction mechanism in which CO dissociation proceeds via a five-coordinate intermediate. This intermediate is structurally very similar to the five-coordinate nitrosyl heme derivative of guanylate cyclase and is presumably responsible for the observed 4-fold activation of guanylate cyclase by CO. Thus, we provide a model that explains enzyme activities of the nitrosyl and carboxy forms of the enzyme on the basis of a common mechanism.     

Determination of pulmonary blood flow by the rebreathing technique in airflow obstruction.

To test the hypothesis that the effect of nonuniform gas distribution on the uptake of inhaled soluble gases in the lung is minimized by rebreathing, we measured pulmonary blood flow by the thermodilution technique, and pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, and alveolar volume by a rebreathing technique in conscious sheep before and immediately after inhalation of a histamine aerosol (4% solution). We also measured pulmonary resistance, distribution of ventilation by multiple-breath N2 washout, and arterial blood gases to monitor airway responses. Histamine inhalation produced a mean pulmonary resistance increase to 621% of baseline accompanied by uneven distribution of ventilation and a decrease in arterial Po2. Despite these alterations in airway function, there were no concomitant changes in pulmonary capillary blood flow, combined pulmonary tissue and capillary blood volume, diffusing capacity of the lung for CO, alveolar volume, or the ratio of diffusing capacity for CO to alveolar volume. Mean pulmonary capillary blood flow and pulmonary blood flow did not differ from each other before and after histamine inhalation. We conclude that the rebreathing technique for noninvasive measurement of pulmonary hemodynamics is satisfactory in the presence of airflow obstruction.     

The prevalence of airflow obstruction in rural primary care

Spirometry has been reported to be under-utilized, and airflow obstruction may be under-diagnosed, in primary care practice. STUDY OBJECTIVES: The objective of this study was to determine the prevalence and severity of airflow obstruction in rural primary care settings and the degree to which it can be predicted by clinical characteristics. Spirometry was performed in patients 35 years and older who had smoked, presenting for any reason to one of eight rural primary care practices. Obstruction was defined as an FEV(1)/FVC<0.70. A total of 1046 subjects were recruited of whom 1034 had acceptable and reproducible spirometry. Airflow obstruction was detected in 17.4% (180 patients). Of those with obstruction, 77.2% (se 3.1%) had at least one respiratory symptom versus 62.4% (se 1.6%) without obstruction (P=0.0002). Only 44.9% (se 3.7%) of those with airflow obstruction had been previously diagnosed with obstructive lung disease. Of those with an FEV(1)<50% of predicted, 85% (se 5.6%) were breathless on exertion; however, only 63% (se 7.6%) were being treated with respiratory medications. We conclude that airflow obstruction is common in rural primary care practice and cannot be accurately predicted by symptoms. It is undiagnosed half of the time, and often not treated even when symptomatic.     

The use of a new breath-actuated inhaler by patients with severe airflow obstruction

The ability of patients with severe airflow limitation (forced expiratory volume in one second less than 1.0 l or peak expiratory flow rate less than 200 l.min.1) to use a new breath-actuated inhaler (BAI) was assessed. One hundred and fifty six patients attending two respiratory units entered and completed the study. Subjects were instructed how to use the device and after attempting to trigger the BAI had flow-volume loops measured. One hundred and fifty one (97%) were able to actuate the inhaler on their first (146) or second (5) attempt. The five unsuccessful patients did not have the most severe airways obstruction. It is concluded that this new device, which is actuated at low inspiratory flow rates, can be used by patients with severe airflow limitation and represents an important advance in inhaler technology.