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Pulmonary complications in acquired immunodeficiency syndrome (AIDS) occur because the human immunodeficiency virus (HIV) has neutralized the cellular defenses of the lung, and in part, the mechanical and inflammatory responses as well. The consequence of this unopposed invasion, is that rare malignant tumors, opportunistic infections, as well as recognized pathogens gain entry into the reluctant host, and culminate in the host's eventual destruction. An acceptable prognosis awaits development of more effective antiretroviral therapy, as well as more efficient specific therapy for MOST of the pulmonary complications.

Sarcoidosis is a disease of unknown etiology characterized by granuloma formation in tissues and anergy to delayed hypersensitivity. In 34 sarcoidosis patients and 16 normal persons, T cells from peripheral blood were quantitated and their functional capacity assessed by sheep red blood cell (SRBC) rosette assay and mitogen response, respectively. Effect of Kveim-Siltzbach suspension (KSS) on rosette formation and its ability to induce blast formation were also examined. Normal spleen cell suspension (NSS) was used as control. The results show that 84% of patients had suppressed T-cell numbers, while 79% had suppression of both active (rosettes formed immediately on incubation with SRBC) and total (rosettes formed after a 1-hr incubation on ice) T cells. Mean active was 30% in sarcoidosis patients vs 44% in controls, while mean total was 48% in sarcoidosis patients vs 64% in controls, while mean total was 48% in sarcoidosis patients vs 64% in control subjects. Suppressed mitogen response to phytohemagglutinin was seen in only 34% of patients and of this number, 90% had decreased T-cell numbers (active and total), suggesting that T-cell suppression does not necessarily reflect functional abnormality in these cells; however, the reverse is true. KSS caused no blastogenesis or change in rosette formation when incubated with lymphocytes from sarcoid patients (KSS active 36%; total 48%: NSS active 34%; total 48%). Either the cells are insensitive to KSS stimulation or sensitive cells have migrated to sites of granuloma formation.

Anatomical and physiologic evidence for pulmonary problems most prevalent in the aged is reviewed. The lungs begin to age in utero. True aging must be distinguished from chronic environmental damage. The lung is essentially an “outdoor organ” vulnerable to the environment. Biochemically, aging is caused by both endogenous and exogenous free radical injury, inflicted by an over-balance of oxidants with respect to anti-oxidants. Glucose may also play a role in the aging process, by binding non-enzymatically with proteins in lung to form irreversible advanced glycosylation end-products. Physiological age-related lung changes result in: decreasing lung volumes and maximal rates of airflow; decreasing forced vital capacity (accelerated in smokers); hyperinflation (confirmed by the increased RV/TLC ratio); increased closing volume or capacity; decreased diffusing capacity; and hyporesponsive respiratory center and peripheral chemoreceptors. The clinical consequence of these age-related changes in the lung is disease in the elderly. Lung cancer and emphysema also occur as a result of chronic exposure to cigarette smoke and other environmental pollutants. Age-dependent pulmonary changes combine with non-pulmonary age-prevalent changes to cause additional diseases. Bacterial pneumonias, aspiration pneumonia, tuberculosis, and pulmonary thromboembolism are examples of these.

Among 80 Black patients with sarcoidosis, 11 families were identified as containing multiple cases. Monogenic modes of inheritance were reasonably excluded by informal inspection of pedigree patterns and by poor fit of corrected ratios within sibships to the expected ratio for all sibships at risk. The observed familial distribution conforms in several respects to properties that are descriptive of multigenic traits. Additionally, heritability based only on female probands was estimated to be between 60% and 70%. A larger sample size should permit analysis of additional multigenic properties.

We studied changes in pulmonary capillary blood volume (Vc) in anesthetized dogs to determine whether 5-HT (5-hydroxytryptamine) constricts pulmonary venules. The preparation was sufficiently stable to allow reproducible measurement of pulmonary diffusing capacity (Dl). A fixed volume of CO gas mixture was introduced into the lungs by positive pressure, and an alveolar sample was obtained after 10 sec. By measuring Dl at different levels of Pao2, a value proportional to Vc was obtained. We cannot give absolute values for Vc since the rate at which CO replaces O2 in red cells in dogs is unknown. In 10 of 14 dogs given 5-HT, Vc increased 6 to 133%. There were no differences in left ventricular diastolic, systemic arterial, or airway pressures. Changes in blood flow were unrelated to changes in Vc. These findings are independent evidence that 5-HT causes pulmonary venous constriction, which in turn leads to passive congestion of the pulmonary capillary bed. Submitted on July 5, 1962

Of 2,357 Negro females tested for tuberculosis during the prenatal period, 9.6 per cent of them had positive reactions (a figure substantially less than that quoted for the general population of the District of Columbia). Except for two known inactive cases of reinfection type tuberculosis, no new pulmonary lesions of this type were found on subsequent x-ray. These results compare favorably with earlier investigations. In a limited study, variation in the amount of tuberculin reaction in women in the pregnant and nonpregnant states appeared to parallel the fluctuations found in nonpregnant individuals. Tuberculin testing of pregnant women is still a valid and most feasible method of case finding and should be continued as long as the incidence of positive reactors indicates a significant reservoir of preinfection. Our findings over a 6 year span suggest a decrease in the the number of pregnant women who were at some time infected by tuberculosis.

Validation of rigid-tube bronchoscopy with small-volume (5-ml increments not to exceed 300 ml) bronchial washing as a therapeutic adjunct was performed on six patients with cystic fibrosis, using serial tests of pulmonary function as a yardstick for assessment of efficacy. Two patients did not undergo the procedure and served as control subjects. All patients were characterized as having varying severity of pulmonary involvement. Large central airways were severely obstructed, and older patients had more trapped gas in their lungs. Hypoxemia and large alveolar-arterial oxygen pressure differences [P(A-a)O2] were due to inhomogeneity of alveolar ventilation. Results indicated that up to ten days to two weeks, bronchoscopic bronchial washing may in some instances improve maximal expiratory flow-volume curves and specific airway conductance and decrease P(A-a)O2 towards normal. Distribution of alveolar gas P(A-a)O2 towards normal. Distribution of alveolar gas became more homogeneous. We conclude that bronchoscopic bronchial washing may be effective in the management of patients with cystic fibrosis, by augmentation of their inadequate cleansing function of the conducting airways.

Verofylline, a long-acting polysubstituted methylxanthine bronchodilator, was taken orally by eight adult patients with asthma in a double-blind, crossover tolerance study. Peak expiratory flow, forced vital capacity, and its subdivisions were measured weekly 2, 4, and 6 hr after oral dosing with drug or placebo. Peak drug activity developed between 4 and 6 hr after dosing. Subject tolerance was good at the doses used. Dose-response curves for mean forced expiratory volume in one second, peak expiratory flow rate, and forced expiratory flow at the end of 4 hr were greater after 0.05 mg/kg verofylline than after placebo or higher doses of verofylline. Mean percent change in forced vital capacity remained increased as long as 6 hr after 0.15 mg/kg active drug. Verofylline was not very effective as a bronchodilator at the doses used.

Pulmonary granulomata of sarcoidosis are composed primarily of mononuclear phagocytic cells that are probably derived from blood monocytes. To evaluate the concept that recruitment of blood monocytes to the sarcoid lung is mediated by chemoattractants produced by immune effector cells within the lung, we obtained mononuclear cells from lung and blood of six patients with active pulmonary sarcoidosis, six normal subjects, and six patients with active idiopathic pulmonary fibrosis and studied their ability to secrete a chemotactic factor for monocytes. Lung T lymphocytes from all sarcoidosis patients, but not from normal subjects or patients with idiopathic pulmonary fibrosis, spontaneously secreted such a mediator. Lung T lymphocytes from patients with sarcoidosis secreted more monocyte chemotactic factor than did blood T lymphocytes from the same patients. The accumulation of monocytes in the lung in patients with pulmonary sarcoidosis may be mediated by local production of monocyte chemotactic factor by lung T lymphocytes.

Cellular and immunoglobulin components of bronchoalveolar fluid recovered by bronchoscopic lavage were evaluated in 32 control patients, 10 normal volunteers, and 60 patients with the following interstitial lung diseases: idiopathic pulmonary fibrosis, pulmonary fibrosis associated with collagen-vascular disease, eosinophilic granuloma, sarcoidosis, and hypersensitivity pneumonitis. The percentage of lymphocytes distinguished two general disease categories: those with increased lymphocytes (sarcoidosis and hypersensitivity pneumonitis); and those with normal lymphocytes (idiopathic pulmonary fibrosis, pulmonary fibrosis associated with collagen-vascular disease, and eosinophilic granuloma). Patients in all five disease categories had elevated IgG levels and percentages of neutrophils compared with control patients, with the highest proportion of neutrophils found in idiopathic pulmonary fibrosis. Immunoglobulin levels also helped distinguish among patient groups, in that patients with hypersensitivity pneumonitis had lavage IgG/albumin ratios greater than 1, whereas patients with sarcoidosis had ratios less than 1; and with infrequent exceptions, the finding of IgM in lavage fluid was limited to patients with hypersensitivity pneumonitis.

Alpha 1 antitrypsin levels measured by the trypsin inhibitory capacity method were increased in a group of 23 patients with active sarcoidosis not under treatment when compared with a group of 17 patients, with inactive sarcoidosis, or age and sex matched healthy controls. Twelve of these patients and two of the control subjects were also studied by the radial immunodiffusion method and cellulose acetate serum electrophoresis methods for measuring a 1 antitrypsin. Obstruction of larger airways was present in 10 of 40 sarcoidosis patients, while the remainder had either a restrictive or normal pattern. In eight patients, measurement of diffusing capacity and a closer assessment for airways obstruction was obtained with measurements of specific airway conductance, thoracic gas volumes, and static and dynamic lung compliance at several respiratory frequencies. Disease of smaller airways was present in six patients as determined by frequency dependence of their dynamic lung compliance. Since three were nonsmokers, airways obstruction was thought to be due to mechanical effects of granulomas. a 1 antitrypsin levels may be another useful determinant of disease activity and may be used to supplement other clinical and laboratory indices of activity.

In Washington, DC, 105 black patients. who had biopsy specimens which confirmed sarcoidosis, were studied clinically. Of these, 16% were asymptomatic while the remainder had a variety of respiratory, constitutional, and other manifestations in agreement with the classical concept of the disease. Twenty-nine patients were in the roentgenographic category of hilar lymphadenopathy bilaterally with or without parenchymal lung infiltration. Seventy-eight patients were anergic to skin-test antigens. Of 33 patients who were Kveim tested, only seven had abnormal biopsy specimens. Patient selection for treatment was based on disease severity. Of the original 105 patients, 64 were observed for five years. The majority improved, but five died. Prognosis was related to both roentgenographic categorization of disease as well as to clinical manifestations.

Spirometric standards have been established for healthy inner-city black children ages 6-14. These are expected to provide better comparisons during pulmonary function testing by hospitals, clinics, and neighborhood health centers during the current decade than previously published values. Since both age and height together, correlated best with vital capacity, minute volume, and maximum voluntary ventilation, regression formulae were constructed from these variables. These standards are intended to be used when testing black children. Comparisons were made with available data for children, and ethnic differences were attributed to both anthropologic as well as socioeconomic factors.