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The clinical significance of an isolated reduction in the carbon monoxide diffusing capacity (DLCO) in nonsmoking, asymptomatic individuals is not known. Whether a reduced DLCO despite otherwise normal pulmonary function tests warrants further investigation remains unanswered. In this article, the authors describe five healthy, asymptomatic, young women who had isolated, reduced DLCO and subsequent follow-up examinations over a span of 6 years. This case series lends support to the contention that an isolated low DLCO in asymptomatic subjects is not clinically significant and does not necessitate additional medical inquiry.
Interstitial lung diseases (ILD) are characterized by an acute or chronic inflammation of the alveolar capillary membrane, which affects the permeability of this membrane. A possible way to measure the permeability of the membrane is by radionuclide aerosol imaging. Pertechnegas, a gas composed of technetium-labelled carbon particles, has recently been proposed as a new ventilation agent to measure this lung clearance. The clearance by pertechnegas in the four most common forms of ILD (eight patients with connective tissue disease, 10 with hypersensitivity pneumonitis, nine with idiopathic interstitial pneumonia and 10 with sarcoidosis) was measured and compared with 10 nonactive smoking controls. Because forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusing capacity of the lung (DL,CO) are used in the assessment of functional severity of the ILD, the pertechnegas clearance was correlated with these lung-function indices. It was found that the time to half clearance of pertechnegas of the lung is significantly decreased in idiopathic interstitial pneumonia (p<0.0001), hypersensitivity pneumonitis (p=0.0005) and connective tissue disease (p=0.002) but not in sarcoidosis when compared with 10 nonsmoking controls. A significant correlation is also found between time to half clearance and FVC (r=0.76; p<0.0001), TLC (r=0.63; p<0.0001) and DL,CO (r=0.75; p<0.0001) for all groups together. For all subjects as a group, the time to half clearance is shorter in the upper lung zones than in the lower zones (p<0.0001) and the ratio between both zones is not significantly different between the different types of disease. These results indicate that pertechnegas clearance is increased in idiopathic interstitial pneumonia, hypersensitivity pneumonitis and connective tissue disease, but not in sarcoidosis and is related to the functional severity of the disease.
Abnormalities in lung function are frequent findings in patients with terminal stage chronic liver disease. While spirometric parameters improve early after liver transplantation, a reduction in diffusion capacity has been reported up to 15 months after transplantation. It is unknown to what extent this disturbance in gas exchange occurs among long term survivors after liver transplantation. We assessed lung function in terms of spirometry, and gas exchange as well as pulmonary morphology by high resolution computed tomography (HRCT) in 40 patients 38 months (median, range 20-147 months) after liver transplantation. The prevalence of restrictive or obstructive changes was not different from predicted values. For the whole group of long-term survivors the carbon monoxide transfer coefficient (KCO) was reduced to 71.3 + 12.0% predicted (P < 0.05). HRCT revealed interstitial changes in only 2/40 (5.0%), emphysematous bullae in 2/40 (5.0%) and pleural thickening in 9/40 (22.5%). Diffusion abnormalities are prevalent in the majority of patients after liver transplantation, whereas spirometric abnormalities are absent also in the long term. The high prevalence of impaired gas exchange and the absence of interstitial lesions imply that changes in pulmonary blood vessels are the most likely cause.
A 49-year-old woman presented with pulmonary hypertension, profound arterial hypoxemia, and a single-breath carbon monoxide diffusing capacity (DLCO) which was 17% of predicted. History, physical examination, and chest roentgenograms did not suggest the presence of parenchymal pulmonary disease. Spirometry and lung volume measurements were within normal limits. Pulmonary veno-occlusive disease was diagnosed by lung biopsy. This case illustrates the severe reduction of DLCO which can be associated with pulmonary veno-occlusive disease.
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We investigated acinar airway involvement in 20 patients with stable asthma, using the phase III slope analysis of the multiple breath N2 washout previously applied in a group of patients with COPD (Am. J. Respir. Crit. Care Med. 1998;157:1573-1577). This technique quantifies severity of conductive and acinar components of ventilation maldistribution separately, through indices S(cond) and S(acin), which increase when respective ventilation inhomogeneities increase. We also investigated the effect of salbutamol inhalation on S(cond) and S(acin) in patients with asthma and compared it with that obtained in patients with COPD. Baseline measurements in the patients with asthma show that (1) acinar ventilation inhomogeneity was indeed abnormal in patients with asthma (S(acin) = 0.195 +/- 0.026 L-1) despite the normal diffusing capacity in this group; S(acin) values were intermediate between those obtained in unaffected individuals and patients with COPD, and that (2) conductive ventilation inhomogeneity was abnormal in the patients with asthma (S(cond) = 0.076 +/- 0.006 L-1) but similar to that obtained in the patients with COPD. Measurements after salbutamol inhalations showed significant changes in S(cond) and S(acin) only in the patients with asthma (p < 0.001). This study primarily demonstrated significant, but partially reversible, acinar airway impairment in patients with asthma, as compared with the more severe baseline acinar airway impairment in patients with COPD, which was not reversible after salbutamol inhalation.
Lymphoid interstitial pneumonitis (LIP) involves a clinicopathologic pattern of pulmonary disease characterized by diffuse interstitial reactive lymphoid infiltrates. In adults, it occurs most commonly in autoimmune diseases, such as Sjögren's syndrome (0.9% of these patients) and primary biliary cirrhosis, whereas in children it is usually seen in HIV infection. Dysproteinemias (hyper- and hypogammaglobulinemia) are found in more than 60% of patients. Children can show CD8-lymphocytosis in bronchoalveolar lavage fluid, lung tissue, peripheral blood, and salivary gland, associated with HLA-DR5 haplotype. Radiographically, most patients with LIP have reticulonodular infiltrates, with or without patchy areas of consolidation. CT scans can show both small nodular and ground glass patterns, patterns that are diagnostically nonspecific. Reduced lung volumes and diffusing capacities are consistent and sensitive indicators of disease in LIP. In an experimental model, diffusing capacity was the single most sensitive functional index of disease progression. Microscopically, LIP is part of a spectrum of pulmonary lymphoid proliferations, ranging from follicular bronchitis-bronchiolitis and pulmonary lymphoid hyperplasia (the latter in AIDS patients), proliferations largely limited to airways, to low-grade malignant lymphoma. These patterns may be difficult to differentiate from each other. It appears that LIP sometimes evolves to lymphoma; the frequency of this evolution is probably low but is difficult to assess because low-grade lymphomas may mimic LIP. A relatively high frequency of LIP patients have Epstein-Barr virus DNA in their lungs but not all patients with LIP show this finding, suggesting other possible etiologies.
STUDY OBJECTIVE: Diffusing capacity of the lung for carbon monoxide (DLCO) is frequently assessed as part of a thorough pulmonary function assessment in patients with pulmonary or cardiopulmonary diseases. However, little information regarding the longitudinal trends of DLCO is available. In this study, we examined the temporal trends in DLCO to determine the effects of smoking and changes in smoking habits. DESIGN: A longitudinal study was recently conducted in the Po River Delta area of northern Italy, in which DLCO measurements were taken approximately 8 years apart in the same subjects; this offered the unique opportunity to assess the temporal changes in DLCO. The longitudinal DLCO data were analyzed independently in two age groups (20 to 40 years, and > or = 40 years) using a repeated-measures analysis. RESULTS: Included were 928 subjects > 20 years old who had DLCO assessments both at baseline and follow-up. Male subjects had higher mean levels of DLCO than female subjects in the older age group (> or = 40 years). Continuous smokers had significantly lower DLCO levels than "never-smokers," but their changes in DLCO during follow-up were the same. This suggests that the lung damage due to smoking had occurred prior to DLCO testing. We also found that the annual decline in DLCO accelerated with age in adults > or = 40 years old. CONCLUSIONS: We conclude that in adults > or = 40 years of age from the general population, DLCO accelerates downwards regardless of gender, smoking, and initial FEV(1) level.
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UNLABELLED: The alveolar integrity (AI) in 17 male patients with pulmonary emphysema (EMPH) diagnosed by chest x-ray was measured by 99mTc-DTPA and 99mTc-HMPAO radioaerosol inhalation lung scintigraphy. METHODS: The patients were divided into two groups: (A) nine patients with pulmonary emphysema and normal carbon monoxide diffusion capacity (DLCO) and (B) eight patients with pulmonary emphysema and abnormal DLCO. The degree of AI damage in EMPH was presented as the slope of the time-activity curves from the dynamic left lung imagings in DTPA and HMPAO. The AI of EMPH patients were compared with the AI of 16 normal controls. RESULTS: The results show that: (1) the slope of DTPA is larger than that of HMPAO in each of the portions of the left lung for any of the study groups; (2) statistical differences were found between the normal controls and EMPH patients in HMPAO but not in DTPA; and (3) the correlation was not good between DLCO and DTPA/HMPAO in EMPH patients. CONCLUSION: Our results suggest that: (1) at least two different mechanisms in the lungs were at work; (2) the AI damage in EMPH developed mainly in the lipophilic part of the alveoli; and (3) the AI damage presented as slopes of DTPA/HMPAO in our study was different from the traditional pulmonary function such as DLCO.
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We have undertaken rebreathing measurements of functional residual capacity (FRC), carbon monoxide diffusing capacity (DLCO), and diffusing coefficient (KCO) during positive pressure ventilation in 15 patients with adult respiratory distress syndrome (ARDS). Measurements of oxygenation (PaO2:FIO2 ratio) and lung injury score (LIS) were also recorded. Eight patients subsequently died (mortality of 53%). There was no significant difference in mean FRC, PaO2:FIO2, or LIS at presentation between survivors and nonsurvivors. However, both DLCO and KCO at presentation were significantly greater in survivors than nonsurvivors. In a separate study of nine patients with less severe lung injury, pulmonary capillary blood volume, derived from values of DLCO measured at two different values of FIO2, correlated with invasive pulmonary vascular resistance (PVR) measurements (r = 0.84, p < 0.01). DLCO measurements can be successfully undertaken in patients being ventilated with acute lung injury and may be a useful, noninvasive method of assessing the pulmonary circulation. The lowest values of DLCO were recorded in patients who subsequently did not survive.
Non-ventilated lung volume (trapped air) during tidal breathing and several other lung function parameters were determined in 19 patients with extrinsic allergic alveolitis, most of them with farmer's lung, and in 28 non-smoking healthy subjects. The trapped air was significantly larger (p < 0.01) in the patients (mean 0.73 litres) than in normal subjects (mean 0.32 litres); in 7 patients (37%) it was definitely enlarged. The results suggest that the frequent increase of trapped air may be caused by patchy small airways occlusion due to bronchiolitis.