The possibility that viral infections of the respiratory tract might predispose to bacterial colonization or infection was studied in 120 patients with chronic obstructive pulmonary disease and 30 control subjects; these individuals were observed for seven years. The ratio of the number of observed to the number of expected associations between viruses and bacteria was 2.43 (P = 0.037) for the pair influenza virus and Streptococcus pneumoniae and was 2.06 (P = 0.056) for influenza virus and Haemophilus influenzae. Consistently positive, but not significant, associations were detected between rhinovirus and herpes simplex virus infections and isolations of S. pneumoniae and H. influenzae. In contrast, isolations of the nonpathogenic Haemophilus parainfluenzae could not be related to prior viral infections. Significant rises in titer of antibody to H. influenzae were detected on 76 occasions, and 20 (26%) of these antibody rises were associated with viral or mycoplasmal infections during the preceding 120 days. The expected number of such associations was 8.34 (ratio of number observed to number expected, 2.40; P = 0.08). These results suggest that viral infections of the respiratory tract in patients with chronic obstructive pulmonary disease are associated with increased colonization by potentially pathogenic bacteria and may also predispose to infections with H. influenzae.

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The effect of 100 separate viral infections of the respiratory tract on pulmonary function was evaluated prospectively over an eight-year period in 84 patients with chronic obstructive pulmonary diseases and in eight normal subjects. Some viral infections were associated with small acute declines in forced vital capacity and/or 1-sec forced expiratory volume of 25-300 ml. These declines were detectable only during the 90-day period after infection. The greatest abnormalities of pulmonary function followed infections with influenza virus, and the mean acute changes in 1-sec forced expiratory volume (-118.5 ml) were significantly greater than expected (-15.2 ml; P = 0.03). Smaller, statistically insignificant declines followed infections with parainfluenza virus, rhinovirus, adenovirus, and respiratory syncytial virus, and no changes were detectable after infections with coronavirus, herpes simplex virus, Mycoplasma pneumoniae, and Haemophilus influenzae. Long-term effects of influenza or other viral infections on the course of chronic obstructive pulmonary disease were not detected in this study population.

The growth of tubercle bacilli in serum samples of untreated animals depends upon the availability of ionic iron which serves as a growth factor in supporting bacillary multiplication. The amount of available iron in serum is determined by the ratio between iron-saturated and iron-free transferrin; a low value for the ratio is associated with tuberculostasis (e.g., human serum, 0.4), whereas a high value is associated with the growth-supporting quality (e.g., guinea pig serum, 5.6). The treatment of guinea pigs with lipopolysaccharide of Escherichia coli or tuberculous cell wall material consistently and significantly reduced serum iron levels; a similar but less striking effect was observed in BCG-vaccinated animals. Pronounced differences were observed in the time of appearance and duration of serum hypoferremia; in lipopolysaccharide-treated animals, it appeared in 1 day and lasted for several days, whereas in BCG-vaccinated animals it appeared in about 2 weeks and lasted for much longer time periods. The induced hypoferremia was always associated with the concomitant development of serum tuberculostasis which could be neutralized by the addition of iron. These results indicate, therefore, that the mechanism of induced serum tuberculostasis in lipopolysaccharide- or tuberculous cell wall-treated and BCG-vaccinated guinea pigs is the same as that present in tuberculostatic sera of untreated animals.

Tubercle bacilli exposed to an iron-poor medium multiplied at a slower rate but released more of the serum-tuberculostasis neutralizing factor (TNF) than the bacilli in an iron-rich medium. This growth-promoting factor found in spent medium exhibited characteristics which suggested its relationship to or identity with mycobactin. The identity of these two bacillary products was established by showing that both iron-free mycobactin and TNF promoted bacillary multiplication in tuberculostatic serum. This study resolved a long-standing controversy as to whether mycobactin serves as a growth factor or as a carrier of iron for tubercle bacilli. It was found that the tuberculostasis in mycobactin-neutralized serum was reconstituted by the addition of iron-free transferrin (Tr). The investigation of the interplay between mycobactin and Tr revealed that mycobactin does not serve as a growth factor but as a carrier of growth-essential iron which mycobactin (as contrasted to Tr) providesto,tubercle bacilli in a utilizable form.