Carbon Monoxide Transfer Coefficient Research Articles

Transfer factor (diffusing capacity) standardized for alveolar volume: validation, reference values and applications of a new linear model to replace KCO (TL/VA)

Transfer factor (TL) varies with alveolar volume (VA), but not in the manner implied by the carbon monoxide transfer coefficient (KCO (TL/VA)). This paper considers two other simple models (one linear and one exponential) which might standardize TL for VA, and asks the questions: 1) Is either model valid? 2) What are appropriate reference values? and 3) Will the model be useful? The relationship of TL to VA within subjects at different depths of inspiration, and between subjects having lungs of different sizes, were measured and compared. The subjects were asymptomatic, nonsmoking, Caucasian adults, including 31 males assessed in the laboratory and 503 male and female participants in population studies. The linear partial regression coefficients of TL on VA (L corrected for body temperature, atmospheric pressure and water saturation (BTPS)) standardized for height (H) in metres, were similar within- and between-subjects; the coefficients applied over a wide range of values for VA. This was not the case for the exponential model. The resulting reference equations in SI units for males and females were: TL = 11.52 H + 2.72 VA.H-2 - 0.051 Age -12.35. RSD 1.17; and TL = 4.87 H + 2.29 VA.H-2 - 0.019 Age -3.03. RSD 0.92, respectively. The residual standard deviations (RSD) about the new relationships were less than in other series. The new linear model could account for much of the variation between different published reference values for TL; it could be useful clinically, in circumstances when VA deviates from the norm. The model does not explain differences in TL associated with gender. Inclusion of VA.H-2 as a covariate in the reference equation for transfer factor, in addition to age and height, improves the accuracy of prediction of normal transfer factor compared with current reference values; its use suggests that some of the differences between published values is due to the volume term. The equations can be used clinically, and eliminate the need for carbon monoxide transfer coefficient.

Pulmonary diffusion impairment following heart transplantation: a prospective study

The aim of this prospective study was to confirm whether and when a fall in gas transfer occurs following heart transplantation (HT); and to examine the potential relationship between gas transfer and haemodynamic change, immuno-suppression and cytomegalovirus (CMV) infection. The lung physiology of 34 heart transplant recipients (HTR) and 14 control patients undergoing coronary artery bypass grafting (CABG) were studied. The absolute and standardized residual values of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), residual volume (RV), forced residual volume (FRC), total lung capacity (TLC), transfer factor of the lungs for carbon monoxide (TL,CO) and carbon monoxide transfer coefficient (KCO) were measured before and at 30, 60, 90, 120 and 150 days after HT. These data were compared to haemodynamic status, graft rejection, cyclosporin levels and episodes of CMV infection. Lung function was studied in a group of patients before and 4 weeks after CABG. There was a significant fall in mean KCO after HT (pre-HT = 1.29 and post-HT = 1.06 mmol.min-1.kPa.L-1) but not after CABG (pre-CABG = 1.49, post-CABG = 1.5 mmol.min-1.kPa.L-1. No relationship was observed between gas transfer and CMV. At the latest stage following HT (150 days) there was a positive correlation between TL,CO (absolute value and standardized residual) and mean cyclosporin level (r = 0.48 and r = 0.44, respectively) and also between the absolute KCO and actual (r = 0.56) and mean (r = 0.55) cyclosporin levels. Following HT, there is an early fall in gas transfer, which is independent of the effects of surgery and bypass, implicating early immunosuppression (e.g. antithymocyte globulin/cyclosporin).

Pulmonary function abnormalities in type I Gaucher disease.

The purpose of this study was to determine the prevalence of pulmonary function and radiographic abnormalities among patients with type I Gaucher's disease, and to analyse the relationship between the pulmonary involvement and genotype and clinical severity score. All patients attending the Gaucher clinic at the Shaare Zedek Medical Center, Jerusalem, Israel, during the years 1992-1993 were prospectively evaluated. Each patient had pulmonary function tests, chest radiography, clinical assessment in terms of degree of organ involvement, and genotype analysis. Of the 95 patients included in the study (mean +/- SD age 29 +/- 15 yrs), 68% had some pulmonary function abnormalities, most commonly a reduced FRC and transfer coefficient for carbon monoxide (Kco), found in 45% and in 42% of the patients respectively. Total lung capacity (TLC) was reduced in 22% of the patients and forced expiratory flows in approximately one third of the patients. Signs of airtrapping (elevated residual volume (RV) or RV/TLC) were seen in 18% of the patients. Males had a higher incidence of reduced expiratory flow than females, (forced expiratory volume in one second (FEV1) was reduced in 36% of males vs 5% of females). Chest radiographic abnormalities were found in 17% of the patients, although only 4% had severe changes. Patients with abnormal pulmonary function had a significantly higher severity score index than those with normal pulmonary function tests. There was no association between abnormal pulmonary function and genotype or age. In conclusion, abnormal pulmonary function is common among type I Gaucher patients. Pulmonary function tests show airways obstruction, with reduced expiratory flows, reduction in lung volumes and alveolar-capillary diffusion abnormality. The rate of progression and the clinical significance need to be determined.

Effects on pulmonary function of two regimens of chemotherapy for AIDS related Kaposi's sarcoma.

We retrospectively analysed serial pulmonary function tests in 14 HIV infected patients receiving either bleomycin and vincristine or liposomal doxorubicin therapy (Doxil) for AIDS related Kaposi's sarcoma. There was a significant reduction in the carbon monoxide transfer coefficient in bleomycin treated patients compared with patients treated with Doxil. No other significant changes in pulmonary function, including the carbon monoxide diffusing capacity, were observed. These preliminary findings suggest that HIV infected patients with Kaposi's sarcoma, who are receiving bleomycin, may be at risk of accelerated pulmonary dysfunction. A larger prospective study should be performed to enable further investigation.

Large lungs and growth hormone: an increased alveolar number?

Previous physiological studies suggest that increased lung growth in patients with acromegaly is associated with either a normal or above normal pulmonary transfer factor. These findings can be interpreted to suggest either alveolar hypertrophy or hyperplasia as the mechanism for lung growth in this condition. Since the ventilated airspaces retain normal elastic properties, we wanted to determine whether the mechanism for lung growth in acromegaly is the result of an increased alveolar number rather than size. Measurements of pulmonary distensibility (K) (an index of alveolar size), elastic recoil, single-breath carbon monoxide transfer factor and carbon monoxide transfer coefficient (KCO), pulmonary capillary blood volume and alveolar membrane diffusing capacity, together with chest width, were compared in nonsmoking, acromegalic and normal men and women, with and without an increased lung size. Pulmonary transfer factor was normal for all groups studied, regardless of lung size. However, KCO was inversely related to total lung capacity (% predicted) for all subjects and KCO (% predicted) was inversely related to chest width in men. Pulmonary capillary blood volume (% predicted) was inversely related to total lung capacity (% predicted) for subjects with large lungs. Pulmonary distensibility (K), membrane diffusing capacity and elastic recoil were within the normal range. These findings suggest normal alveolar size, alveolar membrane surface area and mechanical function in subjects with large lungs. They also suggest that KCO may not be a reliable guide to the interpretation of the mechanism of lung growth in individuals with disproportionately large lungs, and may be reduced because not all the alveoli are perfused. The normal values for pulmonary distensibility found in all our individuals with large lungs, including acromegalics, suggest that lung growth has been achieved by an increased alveolar number rather than size. However, morphometric studies of the lungs of nonsmoking, acromegalic subjects without lung disease, are required to substantiate this finding.

Exercise intolerance in patients with chronic heart failure: role of pulmonary diffusing limitation

In order to test the hypothesis of pulmonary diffusing capacity involvement in exercise limitation in subjects with chronic heart failure (CHF), lung transfer factor (TLCO), oxygen saturation (SaO2), cardiac output (CO) and gas exchange were studied over the course of an incremental exercise test in 10 patients and 10 controls. The TLCO and transfer coefficient for carbon monoxide (TLCO/VA) were measured at rest and during recovery by the single breath method. The SaO2 was followed non-invasively with a finger oximeter and CO was determined according to the carbon dioxide rebreathing method. Analysis of respiratory variables at maximal effort showed significantly lower values in patients with CHF as regards peak oxygen uptake (VO2), minute ventilation (VE), heart rate (HR), oxygen pulse (O2 pulse), and CO with higher ventilatory reserve (VR) than controls. At a comparable workload (30 W), patients with CHF demonstrated higher values for VE and lower values for CO than controls. The TLCO, expressed as percent of predicted values, was significantly lower in CHF patients than controls, respectively, at rest (90.5 +/- 3.75% vs 106.8 +/- 3.8%) and within 5 min after maximal exercise (87 +/- 4.4% vs 117.4 +/- 3.81%). The TLCO/VA showed comparable data between the two groups at rest (81.7 +/- 3.28 vs 90.3 +/- 2.86%). However, significantly lower values of TLCO/VA were obtained for CHF after maximal exercise in comparison to control subjects (77.5 +/- 3.85% vs 96.3 +/- 3.95%). These results confirm the alteration of the main variables in relation to cardiopulmonary exercise limitation in-tHF, and indicate a significant decrease in TLCO and TLCO/VA after maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Single lung alveolar volume and gas transfer: effect of expansion of the other lung.

Temporary occlusion of one mainstem bronchus permits measurement of single lung function. A previous study suggested that the volume at which one lung is occluded may influence the expansion of the other. The effect of ipsilateral occlusion volume on the contralateral effective alveolar volume (VA, EFF,SL), inspired volume (VI,SL), single breath estimated residual volume (RVSB,SL), carbon monoxide (CO) transfer (TLCO,SL) and transfer coefficient (KCO,SL) has been examined. Single breath measurements of CO transfer were made in duplicate in 12 healthy subjects aged 19-44 years, without and during occlusion of one mainstem bronchus by a balloon at RV and at total lung capacity (TLC). Mean VA,EFF,SL, VI,SL, and TLCO,SL were lower during occlusion at RV than during occlusion at TLC (2.84 v 3.26 l; 2.18 v 2.54 l; and 4.70 v 5.51 mmol/kPa/min respectively). RVSB,SL was independent of occlusion volume and KCO,SL not different from the KCO of both lungs (KCO,BL). Single lung values during occlusion at TLC were fairly reproducible and were, except for KCO,SL, approximately half the values for both lungs. During occlusion at RV the second TLCO,SL and KCO,SL were lower than the first. Occlusion of one lung permits reliable determinations of gas transfer indices of the other, provided the lung is occluded at TLC. Occlusion at RV significantly reduces VA,EFF,SL, and hence TLCO,SL, but does not affect KCO,SL of the other lung.

Nutritional depletion in relation to respiratory and peripheral skeletal muscle function in out-patients with COPD

Although increasing attention has been paid to nutritional aspects in chronic obstructive pulmonary disease (COPD), limited information is available regarding the prevalence and consequences of nutritional depletion in a random out-patient COPD population. We studied body composition in relation to respiratory and peripheral skeletal muscle function in 72 COPD patients (mean (SD) forced expiratory volume in one second (FEV1) 53 (15) % predicted), who came to the lung function laboratory for routine lung function measurements. Patients were characterized by the degree of body weight loss and fat-free mass depletion. According to this definition, 14% of the group suffered from both loss of body weight and depletion of fat-free mass, whereas 7% had one of these conditions. We found that tissue depletion was concomitant with lower values for respiratory and peripheral skeletal muscle strength (46.0 (27.2) vs 77.1 (29.8) kg), and a significantly lower transfer coefficient for carbon monoxide (KCO 64.9 (16.2) vs 81.9 (24.5) % pred). Stratification by KCO (< 60% vs > 80%) also revealed significantly lower values for fat-free mass and higher values for intrathoracic gas volumes, total lung capacity (TLC) and residual volume (RV) in the group with a KCO < 60% pred. Analysis of covariance, taking fat-free mass as covariate, indicated an independent contribution of KCO on maximal inspiratory mouth pressure (PImax) but not on peripheral skeletal muscle strength. It is concluded that a substantial number of COPD out-patients suffer from nutritional depletion, preferentially affecting peripheral skeletal muscle function.

Bronchoalveolar lavage immunoglobulin A and G and antiproteases correlate with changes in diffusion indices during the natural course of pulmonary sarcoidosis.

We wanted to determine whether cell populations and soluble components in bronchoalveolar lavage (BAL) could be useful in predicting the outcome of lung function and chest radiography in patients with untreated pulmonary sarcoidosis. Analysis of soluble proteins in BAL fluid, included the levels of immunoglobulins and the two major antiproteases, alpha 2-macroglobulin (alpha 2-M) and alpha 1-protease inhibitor (alpha 1-PI), expressed as a relative coefficient of excretion (RCE). Thirty one nonsmoking patients with biopsy proven sarcoidosis, who remained untreated, had reassessment of lung function tests after 6-54 months (median 21 months). No correlation was observed between initial BAL data and changes in lung volumes and radiographic opacities. By contrast, the initial BAL immunoglobulin A and G (IgA and IgG) RCE correlated inversely with the change in transfer factor for carbon monoxide (TLCO) in the whole group and in patients with sarcoidosis of recent origin (estimated disease duration < 6 months). In the whole group and in patients with longstanding disease (estimated disease duration > 24 months, or radiographic Stage 4), the change in carbon monoxide transfer coefficient (KCO) correlated negatively with the initial alpha 1-PI RCE and positively with the initial helper to suppressor T-cell (T4/T8) ratio. By contrast, no significant difference in BAL cellular and protein data was found between patients with recent and longstanding sarcoidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Health survey of workers occupationally exposed to cobalt

The results are presented for a health control program using 236 male workers exposed to a cobalt inhalation risk. The study group consisted of grinders, producers of diamond tools, workers in metallurgical and mechanical industries (where Widia tools are processed and sharpened), and finally formerly exposed workers. All subjects received a clinical examination, the European Community for Coal and Steel questionnaire on respiratory complaints, a chest X-ray, pulmonary function test, electrocardiogram and determination of urinary cobalt; in 91 subjects, the metacholine bronchial provocation test was performed. Three cases of interstitial lung disease were identified. There were no cases with a significant alteration of ventilatory function while 20 cases (16 exposed and four formerly exposed workers) showed a reduced carbon monoxide transfer coefficient (T L,CO,sb/Va).

Clinical and functional assessment of patients with idiopathic pulmonary fibrosis: results of a 3 year follow-up

The purpose of this study was to analyse the information provided by different techniques used in the assessment of patients with idiopathic pulmonary fibrosis (IPF) and their role in the prediction of lung function decline with the decline. Twenty seven subjects with IPF (55 +/- 14 (mean +/- SD) yrs) were studied at the initial staging. Nineteen of them (70%) were included in a follow-up over 3 yrs (32 +/- 6 months), whilst the remaining 8 patients were lost to follow-up. During the period of the study, 6 of the 19 patients died. A significant correlation between diffusing capacity of the lungs for carbon monoxide (DLCO) (and carbon monoxide transfer coefficient (KCO) = DLCO/alveolar volume (VA)) and the increase in alveolar-arterial oxygen tension difference (A-aPO2) during exercise (delta A-aPO2) was observed at diagnosis (r = -0.58). Despite the treatment with prednisone (1 mg.kg-1 daily during 4 weeks, tapered to an individualized maintenance daily dose of 15-30 mg), the 13 patients controlled throughout the whole period of the study showed a marked impairment in lung volumes; forced vital capacity (FVC) -0.46 +/- 0.09 l, from 69 +/- 16 to 52 +/- 11% of predicted, and total lung capacity (TLC) -0.39 +/- 0.11 l, from 75 +/- 16 to 62 +/- 14%, and in DLCO -0.6 +/- 0.2 mmol.min-1.kPa-1, from 56 +/- 15 to 47 +/- 18%, predicted. By contrast, both mean arterial oxygen tension (PaO2) and A-aPO2 at rest remained unchanged throughout the 3 yrs follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Biologic and clinical effects of continuous infusion interleukin-2 in patients with non-small cell lung cancer

Interleukin-2 (IL-2) has shown antitumor activity in some neoplasms, such as melanoma and renal carcinoma, but toxicity derived from bolus administration is significant, particularly at the cardiorespiratory level. To test feasibility, antitumor activity, pulmonary and systemic immunologic effects, and pulmonary function changes of continuous-infusion recombinant IL-2 given to patients with non-small cell lung cancer, eleven subjects with Stage III-IV disease were treated in a standard pulmonary medicine unit with a dose of 18 million IU/m2/day from day 1 to day 13 with 1-day rest on day 7. A second induction course was given after a 3-week rest. In patients with nonprogressive disease, four maintenance courses of 6 days' duration at the same dose were planned. Immunologic tests, including lymphocyte phenotype analysis and assays for the detection of tumor necrosis factor (TNF) and of anti-IL-2 antibodies, were performed before and after treatment in serum and bronchoalveolar lavage fluid (BAL). Cardiopulmonary function tests, including spirometry, arterial blood gas analysis, diffusion capacity, and echocardiography, were obtained before, during, and after treatment. Twenty-one cycles (15 induction courses plus 6 maintenance courses) were administered. No patient was able to complete the six planned courses, and only 3 patients entered the maintenance phase. Reasons for discontinuation included progressive disease in five cases, toxicity in three cases, and patient request in three cases. The most common side effects were fever, hypotension, oliguria, and elevated serum creatinine and liver enzyme levels. No patient required intubation or intensive care. No objective response was seen, and the median survival time was 10 months. Lymphocytosis and eosinophilia were observed in all patients. Surface marker analysis revealed a statistically significant increase in the percentage of CD3+, CD4+, CD25+ and DR+ cells in peripheral blood. Lymphoid cells derived from BAL disclosed an increased natural killer activity after IL-2 treatment, and TNF was increased in BAL fluid. Pulmonary function tests evidenced an increased alveolar-arterial difference for oxygen allied with a decrease of forced expiratory volume in 1 second, forced vital capacity, and carbon monoxide transfer coefficient consistent with a significant, albeit not clinically relevant, interstitial lung defect. Continuous-infusion IL-2 is feasible in patients with advanced lung cancer even outside an intensive care unit, but overall compliance is poor. Although clinical pulmonary toxicity is negligible, small but statistically significant alterations of the pulmonary function are evident. In addition, this regimen produces a significant activation of the immune system at the pulmonary level.

The contribution of respiratory function tests to clinical diagnosis

The purpose of this study was to investigate the amount of diagnostic information contained in a set of routine lung function studies and to attempt to determine which tests could be omitted without significant loss of discrimination. Cluster analysis was performed on a set of physiological and questionnaire data, collected prospectively in 1,542 male patients, referred consecutively for measurement of forced expired volumes, static lung volumes and measurements of the transfer factor for carbon monoxide. A respiratory questionnaire was completed for each patient. A physician assigned the patients to a rigorously defined diagnostic category, based on supporting clinical information, as well as pulmonary function, apart from 241 patients with unusual diagnoses and those in whom the criteria did not apply satisfactorily. This diagnosis was never included as a classification variable. Basing the classification on three independent measurements, total lung capacity, the ratio of forced expiratory volume in one second (FEV1) to vital capacity, and the transfer factor for carbon monoxide, the computer generated six groups: one normal, one showing an isolated gas exchange defect, and four with varying degrees of restriction and obstruction. This classification performed well in separating the patients with the clinical diagnoses of chronic airflow obstruction, bronchial asthma and interstitial lung disease from those with ischaemic and valvular heart disease and other miscellaneous disorders. Omitting total lung capacity resulted in some loss of specificity, but valid information was still obtained. The inclusion of all the static and dynamic lung volumes and of carbon monoxide transfer coefficient made little difference.(ABSTRACT TRUNCATED AT 250 WORDS)

BAL lymphocyte activation antigens and diffusing capacity are related in mild to moderate pulmonary sarcoidosis

To investigate the relationship [corrected] between immunocytological features of bronchoalveolar lavage (BAL) and clinical indices in sarcoidosis, we studied the lymphocyte subsets, as well as the expression of human leucocyte antigen-DR (HLA-DR) and interleukin 2 receptor (IL-2R) antigens in BAL lymphocytes. We studied 16 patients with untreated sarcoidosis and 12 control subjects. We found significantly higher absolute numbers of lymphocytes bearing the IL-2R antigen in sarcoidosis. A stronger difference between groups was observed in both the percentage and absolute numbers of HLA-DR+ lymphocytes. We also found a moderate but significant correlation between the number of lymphocytes expressing the activation antigens and single breath carbon monoxide diffusing capacity in patients with sarcoidosis: DLCO vs HLA-DR+ lymphocytes (r = -0.60); DLCO vs IL-2R+ lymphocytes (r = -0.62); carbon monoxide transfer coefficient (KCO vs HLA-DR+ lymphocytes (r = -0.53); and KCO vs IL-2R+ lymphocytes (r = -0.58). Our results suggest that the reduction in diffusing capacity, expressed as either DLCO or KCO, results from the severity of alveolitis in mild to moderate sarcoidosis.

Influence of smoking habits on change in carbon monoxide transfer factor over 10 years in middle aged men.

Emphysema is associated with a reduction in carbon monoxide transfer coefficient (TLCO/VA), but little is known about the evolution of changes in TLCO/VA in middle aged smokers at risk of developing chronic airflow obstruction. TLCO/VA (single breath method) was measured on two occasions 10 years apart in 122 middle aged men. Initially TLCO/VA averaged 97% predicted in never smokers (n = 42, mean age 37.2 years), 99% predicted in ex-smokers (n = 21, mean age 41.9 years), and 85% predicted in those who smoked over 15 cigarettes a day (n = 42, mean age 42.0 years). Mean rates of decrease in TLCO/VA over 10 years, however, were similar in the three groups, so that differences between smokers and non-smokers did not increase during the 10 years. Seventeen men (mean age 40.9 years) who initially were smokers became sustained ex-smokers within two years of the first measurement; in these men mean absolute values of TLCO/VA rose, averaging 89% predicted at the first assessment but 102% predicted 10 years later. By the age of about 40 years TLCO/VA was lower in smokers than in never smokers but this difference did not increase over the following 10 years. Sustained ex-smokers had values similar to those of never smokers even when TLCO/VA was known to have been reduced while they were smoking. Changes in TLCO/VA associated with stopping smoking were considerably larger than could be explained by carbon monoxide back pressure, indicating that mechanisms other than irreversible increase in the size of terminal air spaces underlie the lower values in smokers. To detect emphysema in smokers it is necessary to use reference equations that take account of current smoking.

Measurement of carbon monoxide transfer and lung volume in ventilated subjects

A simple method for measuring lung volume and carbon monoxide transfer factor (TLCO) by a rebreathing technique was assessed in nine healthy volunteers undergoing intermittent positive pressure ventilation (IPPV). Measurements of TLCO, alveolar volume (VA) and carbon monoxide transfer coefficient (KCO) made at three inspired oxygen concentrations (21, 35 and 70%) during IPPV were compared to those obtained during spontaneous breathing. The effects of 10 cmH2O positive end expiratory pressure (PEEP) were also studied. Pulmonary capillary blood volume (Vc) and the diffusing capacity of the alveolar capillary membrane (Dm) were derived. There was a close correlation between measurements of TLCO during IPPV (TLCOIPPV) and spontaneous breathing (TLCOSV) (r = 0.92). Ventilated TLCO was 64 +/- 8% of spontaneously breathing TLCO. There was a close agreement between ventilated and spontaneously breathing measurements of KCO (r = 0.95; mean difference 0.14, 95% limits of agreement +0.37 to -0.09 mmol.min-1 x kPa-1 x l-1). Vc was 92 +/- 23 ml during spontaneous breathing and 72 +/- 21 ml during IPPV (p < 0.05). PEEP of 10 cmH2O significantly increased functional residual capacity (2.3 +/- 0.5 to 3.5 +/- 0.6 l) and decreased TLCO (5.9 +/- 1.0 to 5.3 +/- 1.2 mmol.min-1 x kPa-1), KCO (1.7 +/- 0.2 to 1.1 +/- 0.3 mmol.min-1 x kPa-1 x l-1) and Vc (82 +/- 22 to 56 +/- 20 ml). Dm did not change with PEEP. This simple method may be a useful means of assessing gas exchange and lung volume in ventilated subjects. It showed that PEEP increased lung volume but reduced TLCO and that this reduction appeared to be due to a reduction in capillary blood volume.

Diaphragmatic dysfunction in neuralgic amyotrophy: an electrophysiologic evaluation of 16 patients presenting with dyspnea.

We report 16 adult men (age, 41 to 75 yr) with neuralgic amyotrophy (NA) who presented with dyspnea due to involvement of the diaphragm. All patients developed breathlessness after a prodrome of acute severe neck and shoulder pain. Bilateral diaphragm paralysis (BDP) was confirmed in 12 patients and unilateral diaphragm paralysis (UDP) in four by the absence of electrical and mechanical responses to percutaneous phrenic nerve stimulation. Global expiratory muscle strength was well preserved in all patients, but inspiratory muscle strength was reduced in proportion to the extent of diaphragmatic involvement. Lung function showed low lung volumes with preservation of carbon monoxide transfer coefficient in all patients. Two BDP patients were hypoxic (PaO2 = 67 and 54 mm Hg, respectively) on daytime arterial blood gas analysis; the latter patient with pre-existing chronic obstructive pulmonary disease and marked obesity also had borderline hypercapnia (PaO2 = 49 mm Hg). Overnight sleep studies in three BDP and two UDP patients showed frequent intermittent arterial oxygen desaturations apparently caused by obstructive sleep apneas, but there was no evidence of alveolar hypoventilation. Follow-up muscle studies in five BDP and four UDP patients between 2 and 4 yr after initial referral showed complete recovery of diaphragmatic function in only two UDP patients, one of whom relapsed a year later. We postulate that NA may be an important but underrecognized cause of diaphragmatic paralysis in otherwise normal patients. Diaphragmatic strength returns very slowly, if at all.

Regional structure-function correlations in chronic obstructive lung disease measured with positron emission tomography.

Positron emission tomography, performed with isotopes of very short half life, can be used to relate local lung tissue density to local ventilation and to the ventilation:perfusion ratio. This method has been used in 10 patients with severe chronic airflow obstruction and differing values for carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO). Ventilation (VA) and the ventilation:perfusion ratio (V/Q), lung density, and blood volume were measured regionally in a single transaxial section at mid-heart level with the patients in a supine position. Alveolar volume, extravascular tissue lung density, and perfusion (Q) were derived. Twenty five regions with abnormalities in the ventilation images were analysed. Tissue density showed a negative correlation with the ratio V/Q (r = 0.55) and a positive correlation with Q (r = 0.59) and blood volume (r = 0.65). In four patients with a low carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO) < 50% predicted many regions with low VA had low tissue density and normal or high V/Q. On the other hand, in four patients with TLCO and KCO > 50% predicted many regions with low VA had normal or high tissue density and low values of V/Q. The other two patients had patterns between these two extremes. Individual ratios between mean values of tissue density and V/Q had a positive correlation with KCO (% pred; r = 0.79). These findings link structural differences with distinctive functional patterns; they reinforce the view that bronchial inflammation or oedema predominate in some patients with chronic airflow obstruction, whereas alveolar destruction is the major feature in others.

Response to corticosteroids in chronic airflow obstruction: relationship to emphysema and airways collapse

We have studied the relationship between emphysema and airways collapse, and response to corticosteroids in patients with chronic airflow obstruction. One hundred and seven patients completed a placebo-controlled trial comparing 2 wks treatment with oral prednisolone 40 mg.day-1 to inhaled beclomethasone dipropionate 500 micrograms t.d.s. Response to corticosteroids was defined on the basis of changes in forced expiratory volume in one second (FEV1), and/or forced vital capacity (FVC), and/or mean peak expiratory flow (PEF) after treatment. Patients were categorized as those with physiologically defined emphysema (carbon monoxide transfer coefficient (KCO) less than 70% predicted and total lung capacity greater than 120% predicted), and those with pressure dependent airways collapse on the flow-volume loop (ratio of inspiratory to expiratory flow at 50% vital capacity [I:E50] greater than 10). The response to placebo showed a significant order effect, probably due to a carry-over effect of active treatment of at least 3 wks. Hence, the efficacy of active treatment over placebo in the subgroups defined was assessed by analysis of data generated from the first treatment phase of the trial. The presence or absence of physiologically defined emphysema did not affect the response to oral prednisolone. Inhaled beclomethasone dipropionate, however, was less effective in the emphysema group. Pressure dependent airways collapse did not affect the response to either prednisolone or beclomethasone. However, when data from all three treatment phases were analysed there was no significant difference in the response to either drug in any of the subgroups defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic value of lung clearance of 99mTc DTPA compared with other non-invasive investigations in Pneumocystis carinii pneumonia in AIDS.

Various non-invasive investigations were carried out in patients infected with HIV who had respiratory symptoms with and without pneumocystis pneumonia (with pneumonia, n = 13 (five smokers); without pneumonia, n = 22 (13 smokers]. These included chest radiography; lung function tests (forced expiratory volume in one second, forced vital capacity; transfer factor and coefficient for carbon monoxide); arterial blood gas tensions; arterial oxygen saturation at rest and on exercise; and lung clearance of diethylenetriaminepenta-acetic acid labelled with technetium-99m (99mTc DTPA). The effect of scan time (seven v 45 minutes from peak counts) and subtraction of background counts were examined. There were no significant differences between the two groups in lung function tests or arterial blood gas tensions at rest. The median clearance half time of inhaled 99mTc DTPA for the first seven minutes from peak counts was 7.2 minutes for patients with pneumocystis pneumonia and 22 minutes for those without. The median arterial oxygen desaturation on exercise was 5% in patients with pneumocystis pneumonia and 2% in those without. 99mTc DTPA lung clearance was better than the other non-invasive tests in discriminating pneumocystis pneumonia from other pulmonary disorders in patients positive for HIV. A short scan time of seven minutes was as sensitive and specific as the longer scan time of 45 minutes, and this allows the clearance of 99mTc DTPA to become a rapid screening test.