Small airways dimensions in asthma and in chronic obstructive pulmonary disease

The purpose of this study was to compare the dimensions of the peripheral airways in fatal asthma with those from patients with nonfatal asthma, mild COPD, and normal lung function. Lung specimens from eight individuals who had fatal asthmatic attacks were obtained at postmortem and compared with similar specimens from three asthmatic patients who died of an unrelated cause and four specimens obtained from known asthmatic patients who required lung resection for tumor. These 15 asthmatic lungs were also compared with lungs resected for peripheral neoplasms from 15 patients with normal airway function (FEV1, % of predicted > 85) and 15 patients with mild chronic airflow obstruction (FEV1, % of predicted < 85). All membranous airways with a long-short diameter ratio of 3:1 or less were examined. The smooth muscle and the tissue areas external and internal to the muscle layer were traced using a Bioquant BQ System 4. The same system was used to evaluate the fraction of the submucosa and adventitia taken up by blood vessels. The adventitial, submucosal, and muscle area of the asthmatic airways were greater than those of COPD and control (p < 0.01), and the muscle area was greater in COPD than in control lungs (p < 0.05). These parameters were also greater in the 8 patients with fatal asthma compared with the 7 patients with nonfatal asthma (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Self-reported mental distress under the shifting daylight in the high north

Our knowledge of airways reactivity to inflammatory agonists is derived predominantly from tests dominated by large airway responsiveness. To determine directly, the histamine responsiveness of the smallest airways, eight normal and 11 asymptomatic asthmatic subjects were studied utilizing a wedged bronchoscope technique. A fiberoptic bronchoscope was wedged in the anterior segment of the right upper lobe and a double-lumen catheter was advanced through the working channel to its tip. With a constant flow of gas (5% CO2 in air) through one lumen of the catheter, pressure at the tip of the bronchoscope was measured with the subject breath-holding at FRC. Peripheral airways resistance (Rp) was measured at baseline and after saline, histamine (10, 50, 100 mg/ml) and isoproterenol (2 mg/ml) challenge through the bronchoscope. Baseline Rp of asthmatics (0.041 +/- 0.015 cm H2O/ml/min; mean +/- SE) was significantly greater than normal subjects (0.011 +/- 0.003 cm H2O/ml/min; p = 0.019). The log of the concentration of histamine that caused a 100% increase in peripheral airways response was greater in the normal subjects than in the asthmatic subjects (p = 0.0114) and correlated with whole lung responsiveness to histamine in asthmatics (r = 0.847, p < 0.05). Isoproterenol reversed completely the increase in Rp in normal subjects but not asthmatic subjects. The results of this study demonstrate that the resistance of the smallest peripheral airways, when measured directly, increased when challenged locally with histamine in both normal subjects and asthmatic subjects. However, the peripheral airways responsiveness was significantly enhanced in asthmatic subjects relative to normal controls.     

Density dependence of pulmonary resistance: correlation with small airway pathology

The density dependence of maximal expiratory flow is not an effective test of the site of airway narrowing in obstructive lung disease. We hypothesized that the density dependence of pulmonary resistance (DD,RL) would be more closely related to the degree of airway narrowing and peripheral airway pathology in smokers. We measured maximal expiratory flow at 50% vital capacity (V'max50) and lung resistance (RL) breathing air and 80% helium-20% oxygen, and calculated density dependence of V'max50 and RL in 40 patients who had moderate airflow obstruction and in 10 normal subjects. We compared the density dependence of RL and V'max50 with the degree of airway obstruction and bronchiolar pathology scores in 27 patients with resected lung specimens. There were no differences in DD of V'max50 or RL between normal subjects and patients, and no relationship between the degree of obstruction or the bronchiolar pathology score and the DD of these measurements. There were significant relationships between V'max50, RL and the bronchiolar pathology scores. In conclusion, lung resistance and maximal expiratory flow are related to the severity of peripheral airway pathology, but there is no relationship between the severity of obstruction or the severity of peripheral airway pathology and the density dependence of maximal expiratory flow or lung resistance.     

13-cis-retinoic acid or all-trans-retinoic acid plus interferon-alpha in recurrent cervical cancer: a Southwest Oncology Group phase II randomized trial

BACKGROUND: Although previous studies have established the presence of an eosinophil-rich cellular infiltrate in the small airways of asthmatic lungs, the expression of cytokines within the peripheral airways has been largely unexplored. The purpose of our study was to test the hypothesis that TH2-type cytokines are increased in the peripheral airways and parenchyma of asthmatic lungs. METHODS: The presence of messenger ribonucleic acid (mRNA) encoding both T-helper (TH1)-type (IL-2, interferon-gamma) and TH2-type (IL-4, IL-5) cytokines in surgically resected lungs from six asthmatic and 10 nonasthmatic subjects was determined by in situ hybridization. Colocalization of IL-5 mRNA within the large and small airways was performed by simultaneous in situ hybridization and immunocytochemistry. RESULTS: Expression of IL-5 mRNA-positive cells was significantly increased in the large and small airways and in the lung parenchyma of asthmatic subjects compared with nonasthmatic subjects. In the asthmatic individuals, the expression of IL-5 mRNA was increased in the small airways compared with the large airways. There was also an increase in the number of cells expressing IL-4 mRNA in the large and small asthmatic airways compared with the nonasthmatic airways. In contrast, the numbers of IL-2 and interferon-gamma mRNA-positive cells did not differ between asthmatic and nonasthmatic individuals. CONCLUSIONS: We conclude that there is an increased expression of TH2-type cytokines within the peripheral airways of asthmatic lungs and suggest that the small airways contribute to the pathophysiology of asthma.     

Assessing the effect of deep inhalation on airway calibre: a novel approach to lung function in bronchial asthma and COPD

Bronchoconstriction in bronchial asthma and chronic obstructive pulmonary disease (COPD) may be due to decreased airway calibre and/or to the inability of the airways to distend after a deep inhalation (DI). The purpose of this review is to discuss the physiological and clinical relevance of this latter mechanism. During induced constriction, DI shows remarkable bronchodilatation in normal subjects, but a blunted or null effect in asthmatics. In contrast, during spontaneous bronchospasm DI tends to decrease airway calibre. From a functional point of view, airway inflammation, remodelling, and peripheral bronchoconstriction could prevent airway smooth muscle from stretching. Therapeutic intervention improving lung function may change the response to DI. For example, bronchodilators allow expiratory airflow before DI to increase more than after DI, because of decreased bronchial hysteresis. This suggest that bronchodilation might be systematically underestimated from parameters derived from maximal expiratory manoeuvres. Inhaled corticosteroids tend to increase the dilator effect of DI, likely due to decreased bronchial and peribronchial oedema. In conclusion, measuring the effects of deep inhalation on lung function is an easy and simple test able to evaluate the structural changes occurring in the airways and to monitor the effectiveness of therapy.     

The influence of clinical factors on site of airway obstruction in asthma

The effect of breathing a gas mixture less dense than room air (80% helium, 20% 02) on the maximal expiratory flow-volume curve was used to determine the influence of clinical factors on the site and nature of the airway obstruction in asthmatics. If an asthmatic did not smoke or have chronic bronchitis or recurrent respiratory infections, the site of obstruction was in more central airways than it was in the presence of these factors, when the main site was more likely to be in more peripheral airways. Both the peripheral and the central airway obstruction were at least in part due to bronchoconstriction and could be reversed with bronchodilators. Comparison of maximal expiratory flow-volume curves when the subject was breathing air and when he or she was breathing a less dense gas mixture may indicate change in the mechanical properties of the lung after the use of bronchodilators that are not apparent breathing air alone. In some instances, bronchodilators produced no change in the maximal expiratory flow-volume curve when the subject was breathing air, but there were substantial changes when he or she was breathing a mixture of helium and O2.     

Evaluation of periparturient dairy cows and contact surfaces as a reservoir of Cryptosporidium parvum for calfhood infection

To compare the effects of salmeterol, an adrenergic drug, and ipratropium bromide, an anticholinergic drug, on breathlessness and gas exchange during exercise in patients with chronic obstructive lung disease (COPD), we performed a progressive treadmill exercise test on 15 patients on 3 days (24 h apart), after inhalation placebo, ipratropium bromide (120 micrograms) or salmeterol (50 micrograms) in a randomized fashion. Dyspnoea during exercise was evaluated from the regression slope between Borg scale (BS) scores and distance walked each minute on the treadmill. The regression was expressed as the distance walked at BS score 5, the threshold load of dyspnoea (TLD) and breakpoint load of dyspnoea. During and after the exercise, oxygen saturation was monitored by pulse oxymeter and we measured the lower SaO2 during exercise and the recovery time of SaO2 after exercise. In comparison to placebo inhalation we found the same small but significant improvement in airflow limitation after salmeterol or ipratropium inhalation, also the distance walked on treadmill increased after bronchodilators. After bronchodilators the magnitude of oxyhaemoglobin desaturation with exercise was similar to that observed after placebo but the duration of the recovery from sustained SaO2 desaturation after exercise was shorter to the same extent as after ipratropium or salmeterol. Dyspnoeic sensation, when assessed by the TLD and by the distance walked at BS score 5, was decreased after salmeterol and after ipratropium bromide to a similar extent. We conclude that the salmeterol, when given in conventional doses, produces significant improvement in the airway obstruction in the recovery of postexercise HbO2 desaturation and in dyspnoeic sensation in patients with COPD, effects which were similar to those observed after inhalation of the anticholinergic agent ipratropium bromide.     

Time course study for airway inflammation and responsiveness by repeated provocation of aeroantigen in guinea pigs

To investigate the mechanisms of airway hyperresponsiveness (AHR), we examined the time course for asthmatic responses (including immediate asthmatic response (IAR), late asthmatic response (LAR), and AHR), airway inflammation (including edema in the airway, accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF), and mediator release including histamine and thromboxane A2 (TXA2) in BALF after the repeated provocation of aeroantigen in sensitized guinea pigs. Furthermore, we examined the effect of S-1452, a TXA2 receptor antagonist, on the antigen-induced airway obstruction and AHR in guinea pigs. We found that IAR occurred 1 min after every antigen inhalations. LAR was observed every 4 h after the inhalation of antigen without 1st or 2nd challenge. AHR was initially observed 4 h after the 5th inhalation of antigen, and then AHR was observed at every time measured even after the 6th provocation. The water content of the airway increased after the 2nd antigen inhalation. A number of leukocytes, especially eosinophils in BALF, was observed 30 min after the 2nd antigen inhalation. Desquamation of epithelia was observed 30 min after the 5th antigen inhalation. TXB2 and histamine in BALF were detected after the first antigen inhalation. These results suggest that LAR is caused by repeated airway inflammation such as eosinophilia and mediator release including TXA2. AHR may appear with the damages of lung tissue such as desquamation of epithelia. Oral administration of S-1452 (1 and 10 mg/kg) significantly inhibited LAR and AHR, assessed after the 6th antigen challenge. The present findings suggest that repeated antigen challenge causes airway inflammation and leads to the onset of LAR and AHR when became chronic. Furthermore, persistent generated TXA2 plays an important role in the pathogenesis of antigen-induced late-phase obstruction and AHR.     

Relationship of AaDO2 TO AIRWAY PCO2 in dog lungs

We measured the arterial Po2 and AaDo2 in open-chest dogs respired with air and with 5% CO2 in air at various lung volumes using a constant hyperventilatory pattern. The AaDo2 was an inverse function of lung volume with both air and 5% CO2 and was also an inverse function of both alveolar and arterial Pco2 values except at quite high lung volumes. There were two series of closed-chest experiments. In the first series, ventilation was varied to produce alveolar Pco2 and Po2 changes. In the second series, the dogs were hyperventilated at a constant rate and Pco2 was varied by adding CO2 with alveolar Po2 levels kept relatively constant. In both series the AaDo2 was inversely related to Pco2. We conclude that, in dogs, the AaDo2 is independent upon the Pco2 and speculate that this may be related to the effect of CO2 on collateral ventilation, although the Bohr effect may account for some of the dependence.     

Integration of stress research in rheumatoid arthritis: from Alexander to Zautra and back again

Patients with nasal obstruction often have associated snoring. It is uncertain whether surgery, which relieves the nasal obstruction, will also relieve the snoring. We have reviewed 96 patients who complain of both nasal obstruction and snoring and who underwent nasal surgery. Snoring was completely relieved in 48 patients (50%), was less loud in a further 38 patients (40%), unchanged in 8 patients, and louder in 2. Patients who had nasal polypectomy as part of their nasal surgery obtained the greatest snoring relief. The relationship between nasal obstruction and snoring is complex and the alteration of airflow patterns after nasal surgery is postulated to be important in influencing snoring relief. This study suggests that, when snoring and nasal obstruction coexist, nasal surgery should be considered as the first line of surgical treatment.     

Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), on exercise-induced bronchoconstriction (EIB) in children with asthma. Nine asthmatic children (7 boys, 2 girls, with a mean +/- SEM age of 11.0 +/- 0.8 yr) with a history of EIB participated in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body surface area [BSA]) or placebo (0.9% saline) according to a double-blind, randomized, crossover design, and underwent an exercise challenge test 15 min after the pretreatment. Inhaled indomethacin significantly attenuated EIB. The mean maximal percent decrease in FEV1 following exercise was 36.1 +/- 5.7% after placebo and 18.0 +/- 4.6% after indomethacin pretreatment (p = 0.0310). Indomethacin also significantly reduced the mean maximal decrease in arterial oxygen saturation after exercise (p = 0.0378). The inhibition of local prostaglandin synthesis and/or ion transport in the airways may be a mechanism involved in the protective potency of inhaled indomethacin.     

Ventilation and respiratory mechanics during exercise in younger subjects breathing CO2 or HeO2

To determine if ventilation (VE) during maximal exercise would be increased as much by 3% CO2 loading as by resistive unloading of the airways, we studied seven subjects (39 +/- 5 years; mean +/- S.D.) during graded-cycle ergometry to exhaustion while breathing: (1) room air (RA); (2) 3% CO2, 21% O2, and 76% N2; or (3) 79% He and 21% O2). VE and respiratory mechanics were measured during each 1-min increment (20 or 30 W) in work rate. VE during maximal exercise was increased 21 +/- 17% when breathing 3% CO2 and 23 +/- 16% when breathing HeO2 (P < 0.01). Further, the ventilatory response to exercise above ventilatory threshold (VTh) was increased (P < 0.05) when breathing HeO2 (0.89 +/- 0.26 L/min/W) as compared with breathing RA (0.65 +/- 0.12). When breathing HeO2, end-expiratory lung volume (% total lung capacity, TLC) was lower during maximal exercise (46 +/- 7) when compared with RA (53 +/- 6, P < 0.01). In conclusion, VE during maximal exercise can be augmented equally by 3% CO2 loading as by resistive unloading of the airways in younger subjects. This suggests that in younger subjects with normal lung function there are minimal mechanical ventilatory constraints on VE during maximal exercise.     

Effect of acute bicarbonate administration on exercise responses of COPD patients

Patients with severe chronic obstructive pulmonary disease (COPD) are limited in their exercise tolerance by the level of ventilation (VE) they can sustain. We determined whether acutely increasing blood bicarbonate levels decreased acid stimulation to the respiratory chemoreceptors during exercise, thereby improving exercise tolerance. Responses were compared with those obtained during 100% O2 breathing (known to reduce VE in these patients) and to the responses of healthy young subjects. Participants were six patients with severe COPD (forced expired volume in 1 s = 31 +/- 11% predicted) but without chronic CO2 retention and 5 healthy young subjects. Each subject performed three incremental cycle ergometer exercise tests: 1) control, 2) after ingestion of 0.3 g.kg-1 of sodium bicarbonate and 3) while breathing 100% O2. During these tests VE was measured continuously and arterialized venous blood (patients) or arterial blood (healthy subjects) was sampled serially to assess acid base variables. Bicarbonate loading increased standard bicarbonate by 4-6 mmol.L-1 and this elevation persisted during exercise. In both groups, bicarbonate loading resulted in a substantially higher arterial pH; arterial PCO2 was either unchanged (healthy subjects) or mildly (averaging 5 torr) higher (COPD patients). However, in neither group did bicarbonate loading result in an altered VE response to exercise or an increase in exercise tolerance. In contrast, superimposing hyperoxia on bicarbonate ingestion yielded, on average, 24% reduction in VE and 50% increase in peak work rate in the patients (but not in the healthy young subjects). We conclude that acute bicarbonate loading is not an ergogenic aid in patients with severe COPD.     

Inhaled procaterol inhibits histamine-induced airflow obstruction and microvascular leakage in guinea-pig airways with allergic inflammation

BACKGROUND: Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit airway microvascular leakage in experimental animals. This effect may change in animals with chronic airway inflammation. OBJECTIVE: We examined whether inhaled beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic allergic inflammation. METHODS: Three weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled vehicle for OA (saline) for 3 weeks. One day after the last challenge, different doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to animals for 10 min after an anaesthesia. Fifteen minutes after the end of inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6 min and the lungs were removed to calculate the amount of extravasated EB dye into the airways. RESULTS: A significant increase in eosinophil infiltration into the airways was seen in sensitized and challenged animals compared with control animals without sensitization. Among animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited 30 microg/kg histamine-induced increase in EB dye extravasation to a similar degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance (more than 90% inhibition in all groups). The minimal dose of procaterol to inhibit 3 microg/kg histamine-induced microvascular leakage was not different between nonsensitized control animals and those sensitized and challenged for 3 weeks at all airway levels. CONCLUSION: Inhaled beta2-adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.     

Neuroendocrine cell hyperplasia and obliterative bronchiolitis in patients with peripheral carcinoid tumors

Specimens from 25 consecutive patients undergoing lung resection for peripheral carcinoid tumor were examined for evidence of neuroendocrine cell hyperplasia and associated obliterative bronchiolitis. Where available, the CT scans (n = 11) were reviewed for evidence of multiple tumors, and pulmonary function data (n = 16) were reviewed for evidence of airflow obstruction. Nineteen of the 25 patients (76%) had neuroendocrine cell hyperplasia in addition to the dominant carcinoid tumor. Eight patients (32%) had lesions of obliterative bronchiolitis associated with foci of neuroendocrine cell hyperplasia, and two of these patients had asymptomatic airflow obstruction that could not be related to smoking or other lung disease. We conclude that multicentric neuroendocrine cell proliferation is common in patients with peripheral carcinoid tumor of the lung. Associated bronchiolar fibrosis occurs in a high proportion of such patients, but it is usually asymptomatic.     

Functional upper airway obstruction and chronic irritation of the larynx

Wheezing and dyspnoea are typical symptoms of asthma but can also be found in diseases of the extrathoracic airways. Functional upper airway obstruction may imitate, as well as complicate asthma. Functional upper airway obstruction was first described as a conversion disorder in young females with inspiratory stridor. Subsequently, it was found that functional upper airway obstruction was more often a secondary phenomenon in chronic asthma also involving the expiratory laryngeal airflow. During a period of 15 months, we diagnosed six cases of functional upper airway obstruction. Five patients were female and one male, and four were also asthmatics. Three cases showed chronic sinusitis with postnasal drip (PND) and/or gastro-oesophageal reflux. Both disorders may irritate the larynx. Treatment of sinusitis and gastro-oesophageal reflux led to a significant improvement of dyspnoea in all three of these patients. In asthma refractory to treatment and in the case of an asthmatic exacerbation without obvious cause, functional upper airway obstruction should be excluded to avoid unnecessary treatment with systemic steroids. Some of the possible causative factors of functional upper airway obstruction, such as postnasal drip and gastro-oesophageal reflux, are easily treatable.     

Dibutyryl cGMP raises cytosolic concentrations of Ca2+ in cultured nodose ganglion neurons of the rabbit

Airway hyperresponsiveness in asthma has been attributed to impaired ability of deep inspiration (DI) to stretch airway smooth muscle. We have retested this hypothesis by comparing the responses to methacholine of 10 asthmatic and 10 control subjects. After each dose subjects breathed tidally without deep inspiration for 4 min, followed by a forced partial expiration from which flow was measured at a constant volume, 35% baseline VC (Vp 35). This index is independent of both DI and increases in end-inspiratory lung volume (EILV). EILV increased significantly more in the asthmatic group than in the control group (15.0 versus 2.5% of baseline VC, p = 0. 019), a factor that if not taken into account would tend to mask the difference in the two responses. Comparisons were made after a cumulative dose of 50 microg methacholine, which was the highest dose common to all subjects. The asthmatic response was significantly greater than that seen in the control group, with reductions to 25.9 and 72.1% of baseline Vp 35, respectively (p = 0. 0007). We conclude that the sensitivity of asthmatic airways to methacholine is greater than that of normal airways even when DI is prohibited. Therefore, the hyperresponsiveness of asthmatic airways is not attributable simply to an inability of DI to stretch airway smooth muscle.     

Inflammatory cell distribution within and along asthmatic airways

Asthmatic airways are infiltrated with inflammatory cells that release mediators and cytokines into the microenvironment. In this study, we evaluated the distribution of CD45-positive leukocytes and eosinophils in lung tissue from five patients who died with severe asthma compared with five patients with cystic fibrosis. For morphometric analysis, the airway wall was partitioned into an "inner" area (between basement membrane and smooth muscle) and an "outer" area (between smooth muscle and alveolar attachments). Large airways (with a perimeter greater than 3.0 mm) from patients with asthma or cystic fibrosis had a greater density of CD45-positive cells (p < 0.05) and eosinophils (p < 0.001) in the inner airway region compared with the same airway region in small airways. Furthermore, in small airways, asthmatic lungs showed a greater density of CD45-positive cells (p < 0.01) and eosinophils (p < 0.01) in the outer compared with the inner airway wall region. These observations indicate that there are regional variations in inflammatory cell distribution within the airway wall in patients with asthma that are not observed in airways from patients with cystic fibrosis. We speculate that this inflammatory cell density in peripheral airways in severe asthma may relate to the peripheral airway obstruction characteristic of this condition.     

Inhalation of dry-powder mannitol increases mucociliary clearance

Inhalation of hypertonic saline stimulates mucociliary clearance (MCC) in healthy subjects and those with obstructive lung disease. We investigated the effect of inhaling the osmotic agent mannitol on MCC. We used a dry-powder preparation of mannitol British Pharmacopea (BP) which was encapsulated and delivered using a Dinkihaler. MCC was measured for 75 min in six asthmatic and six healthy subjects on two occasions before and after the mannitol inhalation or its control, using 99mTc-sulphur colloid and a gamma camera. The inhaled dose of mannitol was 267+/-171 mg (mean+/-SD) and 400 mg and the percentage fall in forced expiratory volume in one second (FEV1) was 22+/-3 and 4+/-2% in the asthmatic and healthy subjects, respectively. The total clearance in the whole right lung for the 60 min from the start of inhalation of mannitol was greater by 263+/-11.9% in the asthmatic and 18.1+/-4.9% in the healthy subjects compared to the control. The total clearance over 75 min was 54.7+/-9.6% and 33.6+/-9.4% on the mannitol and control day (p<0.002), respectively, in the asthmatic subjects and 40.5+/-7.1% and 24.8+/-7.8% (p<0.002) in the healthy subjects. In conclusion, inhalation of dry-powder mannitol increases mucociliary clearance in asthmatic and healthy subjects and may benefit patients with abnormal mucociliary clearance.     

Noninvasive determination of cardiac output in patients with severe airflow limitation

The noninvasive measurement of cardiac output (Q) by the Indirect Fick CO2-rebreathing technique requires mixed venous P CO2 (P CO2) to be determined by the rebreathing maneuver, and Pa CO2 to be estimated from end-tidal P CO2 (PET CO2). Previous work has suggested that although P CO2 can be determined, Pa CO2 cannot be accurately estimated in patients with significant airflow limitation. Nineteen patients with cystic fibrosis who had severe airflow limitation (%FEV1, 29.3 +/- 7.12 SD) were studied during steady-state exercise at 50% of their measured maximal work capacity. Estimated Pa CO2 was slightly lower than Pa CO2 measured from blood samples obtained from an indwelling arterial catheter (measured: 45.2 +/- 4.92; estimate: 42.7 +/- 5.68 mm Hg). To calculate arterial blood content, the values derived from Pa CO2, pH, hemoglobin (Hb), and O2 saturation were compared with those derived from PET CO2 and O2 saturation, where (1) pH was assumed to be 7.40 and Hb was measured, and (2) pH was assumed to be 7.40 and Hb was assumed to be 15 g/dl (measured mean pH, 7.34; Hb, 14.4 g/dl). No difference in arterial CO2 content was seen between the three methods (measured: 47.53 +/- 5.17; estimate 1: 49.57 +/- 6.58; estimate 2: 49.12 +/- 6.61 ml/100 ml). As pH and Hb can also affect mixed venous CO2 content, the effect on Q was also assessed. Both estimates fit closely with measured Q (r2=0.77 and 0.76), with intercepts not different from zero and slopes not different from 1, and coefficients of variation of 13.5 and 14.6%. When viewed with regard to the confidence intervals for Q as a function of O2 consumption, Q was altered to a minor extent. We conclude that the use of PET CO2 to estimate Pa CO2 can give reasonable values for Q determined noninvasively in patients with severe airflow limitation.