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Background Hypogammaglobulinemia (serum IgG levels Research Question To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD. Study Design and Methods Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status. Results The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P Interpretation Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.

Interleukin-8 (IL-8), a monocyte-derived neutrophil chemoattractant factor, is a polymorphonuclear neutrophil chemotaxin that is involved in a number of inflammatory disorders. Transcription of the IL-8 gene is controlled by regulatory proteins, including nuclear factor-kappaB (NF-kappaB), a family of proteins that is important in the transcriptional control of a number of genes. When cells are activated, NF-kappaB translocates from the cytoplasm to the nucleus, where it activates transcription by binding to a specific sequence within the 5' untranslated region of the gene. During translocation, NF-kappaB is potentially susceptible to diversion by oligonucleotides that contain the binding sequence for this protein. In the current study, we produced phosphorothioate-modified oligonucleotides containing the specific DNA sequence that NF-kappaB binds within the IL-8 gene. We then investigated the effects of transfection of monocytes with these oligonucleotides on interleukin-1beta (IL-1beta)-stimulated IL-8 production, IL-8 mRNA expression, and NF-kappaB binding activity. We found that transfection with these oligonucleotides significantly inhibited monocyte IL-8 production. A single-stranded oligonucleotide with two copies of the NF-kappaB-binding sequence was the most potent of those tested. This single-stranded oligonucleotide also inhibited IL-1beta-induced translocation of NF-kappaB to the nucleus and reduced IL-8 mRNA expression. These studies demonstrated that monocyte production of IL-8 can be attenuated using a single-stranded oligonucleotide that binds a transcriptional activating protein before it translocates to the cell nucleus. This approach ultimately may be useful in the control of inflammation involved in a number of diseases.

An AIDS patient with a cavitary lung lesion was found to have pulmonary malacoplakia associated with Rhodococcus equi infection. The diagnosis was based on the typical histologic features of transbronchial biopsy and a positive bacterial culture. All 13 reported cases of AIDS patients with pulmonary malacoplakia were associated with R equi. The recognition of this unique entity is important because of its responsiveness to therapy.

Administration of more than 40 separate pharmacologic agents has been associated with some form of pulmonary toxicity. This problem is becoming more significant every year. Occasionally, effective modes of therapy must be withdrawn because of undesirable pulmonary side effects, putting patients at risk for potentially lethal diseases. Pulmonary parenchymal damage due to drugs is an especially troublesome problem because irreversible pulmonary disease may occur. Mechanisms of pulmonary parenchymal tissue damage by drugs are unclear. It appears that some drugs induce direct tissue injury in addition to indirect tissue damage through amplification of pulmonary inflammation; other drugs cause pulmonary alterations solely through indirect mechanisms. Common clinical syndromes associated with drug-induced pulmonary parenchymal disease include pneumonitis/fibrosis, hypersensitivity lung disease, and noncardiogenic pulmonary edema. Less common patterns of pulmonary parenchymal injury by drugs include bronchiolitis obliterans and a pulmonary renal syndrome. Risk factors for pulmonary injury due to pharmacologic agents are partially defined but not entirely understood. To date, there are no adequate tests for early detection of pulmonary damage by drugs, although research into this area is active. This review discusses mechanisms and clinical features of drug-induced pulmonary parenchymal injury to aid the clinician in recognizing and understanding these syndromes.