Hypercapnia impairs lung neutrophil function and increases mortality in murine pseudomonas pneumonia.

Hypercapnia, an elevation of the level of carbon dioxide (CO2) in blood and tissues, is a marker of poor prognosis in chronic obstructive pulmonary disease and other pulmonary disorders. We previously reported that hypercapnia inhibits the expression of TNF and IL-6 and phagocytosis in macrophages in vitro. In the present study, we determined the effects of normoxic hypercapnia (10% CO2, 21% O2, and 69% N2) on outcomes of Pseudomonas aeruginosa pneumonia in BALB/c mice and on pulmonary neutrophil function. We found that the mortality of P. aeruginosa pneumonia was increased in 10% CO2-exposed compared with air-exposed mice. Hypercapnia increased pneumonia mortality similarly in mice with acute and chronic respiratory acidosis, indicating an effect unrelated to the degree of acidosis. Exposure to 10% CO2 increased the burden of P. aeruginosa in the lungs, spleen, and liver, but did not alter lung injury attributable to pneumonia. Hypercapnia did not reduce pulmonary neutrophil recruitment during infection, but alveolar neutrophils from 10% CO2-exposed mice phagocytosed fewer bacteria and produced less H2O2 than neutrophils from air-exposed mice. Secretion of IL-6 and TNF in the lungs of 10% CO2-exposed mice was decreased 7 hours, but not 15 hours, after the onset of pneumonia, indicating that hypercapnia inhibited the early cytokine response to infection. The increase in pneumonia mortality caused by elevated CO2 was reversible when hypercapnic mice were returned to breathing air before or immediately after infection. These results suggest that hypercapnia may increase the susceptibility to and/or worsen the outcome of lung infections in patients with severe lung disease.

Hypercapnic acidosis attenuates lung injury induced by established bacterial pneumonia.

BACKGROUND: Hypercapnic acidosis protects against lung injury after ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. The effects of hypercapnic acidosis in the setting of established pulmonary sepsis are not known. The authors investigated whether hypercapnic acidosis -- induced by adding carbon dioxide to inspired gas -- would be beneficial or deleterious in established Escherichia coli pneumonia in an in vivo model, in the presence and absence of antibiotic therapy. METHODS: Adult male Sprague-Dawley rats were anesthetized and ventilated. In the first set of experiments, rats were anesthetized, E. coli (5-6.4 x 10(9)/ml colony-forming units) was instilled intratracheally, and the animals were allowed to recover. After 6 h, during which time a severe pneumonia developed, they were reanesthetized and randomly assigned to normocapnia (fraction of inspired carbon dioxide [Fico(2)] = 0.00, n = 10) or hypercapnic acidosis (Fico(2) = 0.05, n = 10). The second set of experiments was performed in a manner identical to that of series 1, but all rats (n = 10 per group) were given intravenous ceftriaxone (30 mg/kg) at randomization. All animals received normocapnia or hypercapnic acidosis for 6 h, and the severity of lung injury was assessed. RESULTS: In the absence of antibiotic therapy, hypercapnic acidosis reduced the pneumonia-induced increase in peak airway pressure and the decrease in static lung compliance compared with control conditions. In the presence of antibiotic therapy, which substantially reduced lung bacterial counts, hypercapnic acidosis significantly attenuated the extent of pneumonia-induced histologic injury. CONCLUSIONS: Hypercapnic acidosis reduced the magnitude of the lung injury induced by established E. coli pneumonia.

Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care center attendees.

BACKGROUND: Incidence and severity of respiratory infections are increased in day-care center attendees. Streptococcus pneumoniae is an important contributor to these infections. OBJECTIVE: To examine whether the use of a pneumococcal conjugate vaccine could reduce the occurrence of respiratory infections and the ensuing antibiotic drug use in the day care. METHOD: In this double blind, randomized, controlled study performed in 8 day-care centers located in Beer-Sheva, Israel, 264 toddlers ages 12 to 35 months at enrollment were randomized to receive either a 9-valent conjugate pneumococcal vaccine (conjugated to CRM197) or a control vaccine [conjugate meningococcus C vaccine (conjugated to CRM197)] and were followed for an average of 22 months. The main outcome measures were respiratory morbidity and antibiotic use. RESULTS: An overall reduction of 7% in child months with > or = 1 reported illness episodes was observed among vaccinees (P = 0.008), and 85% of all episodes were related to the respiratory tract. Reductions of 15, 16 and 17% were observed in upper respiratory infections, lower respiratory problems and otitis media, respectively. An overall reduction of 17% in antibiotic days was observed [10% for upper respiratory infections, 20% for otitis and 47% for lower respiratory problems (P < or = 0.005 for each entity)]. The reduction in episodes and antibiotic use was greater for those <36 months of age than for the older children. CONCLUSION: The reduction of respiratory problems, including those not traditionally considered of pneumococcal origin and the ensuing lowered antibiotic use in day-care center attendees by pneumococcal conjugate vaccination suggest a broader benefit from the vaccine than preventing invasive disease only.