Pulmonary fibrosis and lung carcinoma: a comparative study of metaplastic epithelia in honeycombed areas of usual interstitial pneumonia with or without lung carcinoma

Usual interstitial pneumonia (UIP), or idiopathic pulmonary fibrosis, has been considered to be associated with a high risk for lung carcinoma. To investigate this well-known but still equivocal relationship, we reviewed the clinical features of UIP autopsy cases with or without lung carcinoma (n = 32 and 38, respectively), and compared the morphology and cell kinetics of metaplastic epithelia in the honeycombed areas (n = 11, each group). Thirty-two of 70 UIP autopsy cases showed lung carcinomas. Clinically, UIP with lung carcinoma showed a male predominance (P = 0.001), a higher rate of smoking history (P = 0.001) and a later onset of UIP (P = 0.02), compared with UIP without lung carcinoma. Most of the carcinomas were peripheral in origin (90%), and 65% were topographically associated with honeycombed areas or the border between honeycombing and non-fibrotic areas. Quantitative assessment of the metaplastic epithelia in the honeycombed areas revealed that squamous metaplasia, but not cuboidal cell metaplasia or bronchial cell metaplasia, occurred more frequently in UIP with lung carcinoma than in UIP without lung carcinoma (P = 0.02). There were no significant differences between the two groups with regard to the labeling indexes of Ki-67 and p53 in the metaplastic epithelia, including squamous metaplasia. The degree of atypical squamous metaplasia was not different between the two groups. The quantitative predominance of squamous metaplasia in the honeycombed areas may not be a precursor for lung carcinoma, but might reflect a constitutional susceptibility of UIP patients to develop a lung carcinoma.     

Sequential respiratory syncytial virus cytomegalovirus pneumonia following bone marrow transplantation

A 6-month-old child with familial hemophagocytic lymphohistiocytosis (FHL) experienced early sequential pneumonia due to respiratory syncytial virus (RSV) and cytomegalovirus (CMV) following bone marrow transplantation (BMT). The patient was deficient in natural killer (NK) cell activity (as found frequently in patients with FHL), and this risk factor may have played a major role in the concomitant infection by the two viral pathogens. Rapid diagnostic methods for both viruses are essential and early specific treatment may serve to ameliorate RSV- and CMV-induced lung injury in these life-threatening infections. © 1995 Wiley-Liss, Inc.     

Cytokine responses to the native and recombinant forms of the major surface glycoprotein of Pneumocystis carinii

Pneumocystis carinii is a major opportunistic pathogen and leading cause of morbidity in patients with AIDS. The major surface glycoprotein (MSG) of P. carinii, represented by a family of related proteins encoded by unique genes, is highly immunogenic and contains T cell-protective epitopes. We undertook the present study to define the CD4 T helper (Th) response by cytokine secretion to native MSG and a recombinant form of the protein, MSG-B. Spleen cells were collected from Lewis rats and restimulated with both native MSG and MSG-B. Within 24 h, the CD4 cells secreted high levels of interferon-gamma (IFN-γ) in response to both types of antigen, indicative of a Th1 response; however, after 72 h of incubation, only the native MSG stimulated secretion of IL-4 (Th2 response) from the cells. We then investigated whether the presence of IL-4 could alter the predominant Th1 phenotype by the CD4 cells in response to MSG and MSG-B. Cells cultured with native MSG and IL-4 produced low levels of IFN-γ and elevated levels of IL-4. Interestingly, cells incubated with MSG-B and IL-4 reduced production of IFN-γ, but were not stimulated to produce increased levels of IL-4. The presence of anti-IFN-γ antibody in the MSG- or MSG-B-stimulated cultures did not effect the expression of IFN-γ mRNA, suggesting that the generation of Th1 cells in response to MSG or MSG-B was not dependent on IFN-γ. We conclude that native MSG, which contains multiple forms of this antigen, and recombinant MSG elicit different cytokine responses in vitro. These data are not only important to studies of MSG, but may also be relevant to the role of MSG in the immunopathogenesis of P.carinii infection in vivo.     

Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response to Pseudomonas aeruginosa lung infection

Polymorphonuclear neutrophils (PMNs) are crucial for the outcome of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis. We compared PMNs and inflammatory cytokines in the lungs and blood from susceptible BALB/c and resistant C3H/HeN mice 1 and 2 days after intratracheal challenge with alginate embedded P. aeruginosa. These parameters were correlated with the quantitative bacteriology and histopathology of the lungs. After challenge, the content of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein-2 (MIP-2) was increased in the lungs and the sera and the percentage of PMNs was increased in the blood. However, 2 days after challenge the concentration of G-CSF and MIP-2 was higher in the lungs and sera of BALB/c mice. CD11b expression was higher on the PMNs of the C3H/HeN mice. The expression of CD62L on PMNs of both strains of mice was decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow and the persistent chemotactic gradient provided by MIP-2 in the lungs.     

Mixed microbial aetiology of community-acquired pneumonia in children

Seven paediatric studies on community-acquired pneumonia with serological methods for both viruses and bacteria have been published, allowing the evaluation of concomitant multiple etiological findings. In these studies, dual viral infection has been present in 0-14%, dual bacterial infection likewise in 0-14%, and mixed viral-bacterial infection in 3-30% of the pneumonia cases. The results confirm former clinical observations that respiratory viruses often pave the way for airway-colonising bacteria. The measured frequency of multiple infections has been dependent on the available test panel, mainly on the tests used for pneumococcal aetiology. Mixed viral-bacterial infections have been especially common in young children under 2 years of age, reflecting the high frequency of respiratory syncytial virus infections and their tendency to induce bacterial co-infections. No microbe-specific viral-bacterial associations have been demonstrated. The clinical implications of mixed viral-bacterial infections, compared with viral infections alone or bacterial infections alone, have so far remained unresolved. Current guidelines recommend antibiotic therapy for all community-acquired pneumonia cases in children.     

Antibodies to pneumococcal polysaccharides in pneumonia and response to pneumococcal vaccination in young children in Papua New Guinea.

Antibodies against pneumococcal polysaccharides were measured by ELISA in Papua New Guinean children with pneumonia aged 0-14 months, in age-matched healthy Papua New Guinean controls and in healthy expatriate children living in Papua New Guinea. At 0-5 months of age, the IgG antibody titres against six of the eight polysaccharides measured were significantly lower in pneumonia patients than in both control groups. Antibody titres in 6-14-month-old Papua New Guinean controls were significantly lower than in control Papua New Guineans aged 0-5 months for five of the eight polysaccharides tested. In the 6-14-months age group the antibody titre was significantly lower in pneumonia patients than in controls for only one polysaccharide. For seven of the eight serotypes tested, antibody levels in expatriate controls did not decline with age. Antibody responses of Papua New Guinean children aged 6-18 months to a 23-valent pneumococcal vaccine were serotype dependent. Fold increases in response to the vaccine were greatest for the IgA isotype. IgG antibody responses were greater than three fold to four of the eight serotypes tested.     

Immunohistochemical labelling of cytokines in lung lesions of pigs naturally infected with Mycoplasma hyopneumoniae

Mycoplasma hyopneumoniae (Mh) is the primary agent of porcine enzootic pneumonia (PEN), a chronic respiratory disease endemic to pig farms, and characterized histologically by infiltration of mononuclear cells in airways and prominent hyperplasia of the bronchus-associated lymphoid tissue (BALT). To gain further insight into the pathogenesis of PEN, cytokine expression in the lung, with particular attention to the BALT, was examined immunohistochemically in pigs naturally infected with Mh. An increase (P < 0.05) in proinflammatory and immunoregulatory cytokines (especially interleukin [IL]-2, IL-4 and tumour necrosis factor [TNF]-alpha, and to a lesser extent IL-1 [alpha and beta] and IL-6) was detected in the BALT, which showed intense lymphoid hyperplasia. IL-1beta and TNF-alpha were also detected in the bronchoalveolar exudate of infected pigs, and IL-6 and IL-8 were demonstrated in mononuclear cells of the alveolar septa. The results showed that in Mh infection, macrophage and lymphocyte activation results in the expression of a number of cytokines capable of inducing lung lesions and lymphoreticular hyperplasia of the BALT.     

围产儿羊水吸入性肺炎发病学探讨：172例多因素逐步回归研究

对1980.9～1982.8江苏省6个城市172例围产儿羊水吸入性肺炎临床病理多因素回归分析研究,以探讨其发病机制。目的是筛选能影响肺炎和羊水吸入的临床参数。结果:(1)男婴占52.91%,女婴47.09%。(2)组织学:肺的炎症和羊水大多数是混合性、弥漫性分布,病变较一致,纤维素渗出很少,这说明本病可能是在出生前或分娩过程中吸入感染的羊水所致。(3)影响本病发生的主要因素为剖腹产、胎吸术、羊水吸入以及胎龄。(4)影响羊水吸入性的因素为胎儿体重(4000g以上)和胎龄(42周以上)。而体重、胎龄和胎吸术又和产程延长有关。     

Cytomegalovirus (CMV) infections in patients receiving CMV-IgG-hyperimmunoglobulin prophylaxis after bone-marrow transplantation

Summary Conditioning therapy with aggressive chemotherapy and irradiation induces a state of transient combined immunodeficiency in bonemarrow transplant recipients. This promotes the occurrence of severe cytomegalovirus (CMV) infections, the most frequent lethal complication after bone-marrow transplantation (BMT) at present.Forty-four BMT recipients received CMV-IgG-hyperimmunoglobulin for CMV prophylaxis intravenously. The efficacy of this prophylaxis and possible risk factors for the occurrence of CMV-induced interstitial pneumonia (IP) were analyzed. Risk factors for the promotion of a CMV-IP were: additional immunosuppressive therapy after BMT, CMV-positive serostatus of the recipient, CMV-seropositive granulocyte transfusion, CMV infection immediately prior to BMT, and HLA-haploidentical BMT. In this study the incidence of graftversus-host disease was low and was not associated with the incidence of CMV infections. The use of T-cell-depleted grafts did not result in increased CMV infections or IP and may possibly have improved the immunological reconstitution.Abbreviations BMT Bone-marrow transplantation - CMV Cytomegalovirus - CMV-IG CMV-IgG-hyperimmunoglobulin - GvHD Graft-versus-host disease - IP Interstitial pneumonia - IS Immunosuppressive therapy