Endogenous opioids and ventilatory responses to hypercapnia in normal humans.

Though administration of opioid peptides depresses ventilation and ventilatory responsiveness, the role of endogenous opioid peptides in modulating ventilatory responsiveness is not clear. We studied the interaction of endogenous opioids and ventilatory responses in 12 adult male volunteers by relating hypercapnic responsiveness to plasma levels of immunoactive beta-endorphin and by administering the opiate antagonist naloxone. Ventilatory responsiveness to hypercapnia was not altered by pretreatment with naloxone, and this by itself suggests that endogenous opioids have no role in modulating this response. However, there was an inverse relationship between basal levels of immunoactive beta-endorphin in plasma and ventilatory responsiveness to CO2. Furthermore, plasma beta-endorphin levels rose after short-term hypercapnia but only when subjects had been pretreated with naloxone. We conclude that measurement of plasma endorphin levels suggests relationships between endogenous opioid peptides and ventilatory responses to CO2 that are not apparent in studies limited to assessing the effect of naloxone.

Morphologic-physiologic correlates of the severity of fibrosis and degree of cellularity in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of lung parenchyma characterized by a chronic inflammatory cellular infiltration and varying degrees of interstitial fibrosis. Current data indicate that the severity of fibrosis and the degree of cellularity determine, in part, the prognosis of IPF and the response to therapy. Whereas lung biopsy gives the best assessement of fibrosis and cellularity, physiologic studies are used to stage and monitor the disease process. To determine which physiologic studies correlate best with severity of fibrosis and degree of cellularity, these parameters were graded in lung biopsies of 23 patients with IPF and compared with a variety of physiologic studies. Although vital capacity, total lung capacity, and diffusing capacity are commonly used as objective monitors of the disease process, none of these parameters correlated with either the severity of fibrosis or the degree of cellularity in biopsy specimens. In contrast, almost all parameters of lung distensibility correlated with the morphologic assessment of degree of fibrosis; compliance had the best correlation. Parameters of distensibility, however, correlated poorly with the degree of cellularity. In comparison, gas exchange during exercise correlated with both morphologic parameters; the exercise-induced changes in arterial oxygen pressure per liter of oxygen consumed had a high correlation with the degree of fibrosis (r = 0.89; P less than 0.001) and correlated to a lesser extent with the degree of cellularity (r = 0.56; P = 0.009). In contrast, neither the resting arterial oxygen tension nor the arterial oxygen tension at maximal exercise correlated with the morphologic assessment of degree of fibrosis or the degree of cellularity. These morphologic-physiologic comparisons suggest that (a) lung volumes and diffusing capacity are poor monitors of both the degree of fibrosis and the degree of cellularity; (b) the fibrotic process contributes, at least in part, to parameters of lung distensibility, and both fibrosis and cellularity contribute to gas exchange alterations during exercise; and (c) parameters of lung distensibility and exercise-induced gas exchange alterations may be useful in staging the severity of disease in IPF.

Distribution of HLA antigens in idiopathic pulmonary fibrosis.

Divergent observations suggest that genetic factors contribute to the susceptibility to or clinical course of idiopathic pulmonary fibrosis. To determine whether there is an association between the major histocompatibility (HLA) system and idiopathic pulmonary fibrosis, the distribution of 35 antigens of HLA loci A and B was determined among 33 white patients with idiopathic pulmonary fibrosis and 329 healthy white control subjects. Although certain antigens tended to be more prevalent among patients with idiopathic pulmonary fibrosis compared with control subjects, there were no significant differences in the phenotype frequencies of the HLA-A and HLA-B antigens between these 2 groups. Thus, although subtle associations may exist between the HLA loci and idiopathic pulmonary fibrosis, these results indicate that antigens of the HLA-A and HLA-B loci are not linked with major risk factors in this disease.

Small airways in idiopathic pulmonary fibrosis. Comparison of morphologic and physiologic observations.

18 patients with idiopathic pulmonary fibrosis were studied to determine if they had morphologic evidence of small airways disease and if physiologic testing could predict morphologic findings. In the presence of normal airway function by standard physiologic studies (forced expiratory volume in 1 s/forced vital capacity and airway resistance by plethysmography), dynamic compliance, maximum expiratory flow-volume curves, and maximum flowstatic recoil curves were measured to detect physiologic alterations consistent with small airways abnormalities. These physiologic data were then compared with estimates of small airways diameter made in lung biopsy specimens.94% (17 of 18) of the patients had peribronchiolar fibrosis or peribronchiolar inflammation or bronchiolitis. 67% (12 of 18) had an overall estimate of small airways diameter of "narrowed," whereas 33% (6 of 18) had airways that overall were "not narrowed." 59% (10 of 17) had frequency-dependent dynamic compliance, 50% (9 of 18) had abnormal maximum expiratory flow-volume curves, and 39% (7 of 18) had abnormal maximum flow-static recoil curves. Comparisons between morphologic and physiologic data revealed a significant correlation between the results of dynamic compliance and the overall estimate of small airways diameter (P = 0.001), and the results of maximum flow-volume curves and the overall estimate of small airways diameter (P = 0.009); there was no significant correlation between the results of maximum flow-static recoil curves and the overall estimate of small airways diameter (P = 0.1). THE RESULTS OF THIS STUDY SUGGEST THAT: (a) idiopathic pulmonary fibrosis is a disease of small airways as well as alveoli; (b) dynamic compliance and the maximum expiratory flow-volume curve can predict the overall status of small airways diameter in idiopathic pulmonary fibrosis; and (c) whereas the maximum flowstatic recoil curve predicts the overall estimate of small airways diameter in most patients with this disease, it is the least sensitive of these three monitors of small airways.