Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies

INTRODUCTION:

Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown.

OBJECTIVES:

The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure.

METHOD:

Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression.

RESULTS:

Bacterial bronchopneumonia was present in 33.9% of the cases and cancer in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7% (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis.

CONCLUSIONS:

Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.     

Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure: demographics, etiologic and pulmonary histologic analysis

OBJECTIVES:

Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life.

METHODS:

This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression.

RESULTS:

In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema.

CONCLUSIONS:

For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has not previously been reported.     

Urokinase plasminogen activator and TGF-beta production in immunosuppressed patients with and without P. Jiroveci infection

Macrophages play a pivotal role in a host's defence against pulmonary infections. Macrophage functions are impaired in immunosuppressed (IS) patients, regardless of whether they are HIV-positive (HIV+) or -negative (HIV-). Several studies have indicated that urokinase plasminogen activator (uPA) and transforming growth factor beta (TGF-beta) are important factors in a host's defence against pulmonary pathogens. We measured uPA and TGF-beta activity in unstimulated peripheral blood monocytes (PBM) of both HIV-infected and non-infected IS patients with or without Pneumocystis jiroveci (formerly carinii) pneumonia (PCP). As previously found in alveolar macrophages (AMs), the majority of uPA activity was found in cell lysates. The highest values of uPA activity were found in control subjects. All the patients displayed a decreased production of uPA, irrespective of HIV infection. Similarly, active TGF-beta was higher in control subjects than in HIV+ and IS patients. The presence of P. jiroveci infection further lowered uPA and TGF-beta activity. Decreased TGF-beta activation might be a consequence of lower uPA production, which may, in turn, influence virus replication, since it has been demonstrated that TGF-beta can suppress human HIV expression in monocytes/macrophages. Further studies are warranted to elucidate whether the decrease in uPA and TGF-beta activity impairs a host's defence against P. jiroveci infection.     

Spectrum of pathologic manifestations of Pneumocystis carinii pneumonia in patients with neoplastic diseases

Pneumocystis carinii is the most common protozoan organism causing infection in immunosuppressed patients. This study, based on a review of 32 lung biopsies and 13 autopsies of patients with neoplastic diseases who developed P carinii pneumonia, emphasizes the morphologic variation of this disease. Excluded from this study are those patients with PCP secondary to bone marrow transplantation and AIDS. P carinii pneumonia occurred predominately in patients with malignant lymphoreticular neoplasms, 73% of those in our series, and the remaining 27% had solid tumors. There were 27 males and 18 females and their ages ranged from 1 to 73 years, with a median age of 30 years. Microscopically, the diagnostic intraalveolar foamy exudate of P carinii pneumonia was present in only 58% of the cases. Furthermore, diffuse alveolar damage alone was present in 26% of cases. This change was especially prominent when the characteristic foamy material was scanty. Other tissue reactions to P carinii included the presence of giant cells, epithelioid granulomas, desquamative interstitial-like pneumonitis, and interstitial lymphoid infiltrate. Extrapulmonary dissemination was not observed in this patient population. The pathologist should be aware of the marked variations that occur in the morphologic appearance of PCP, and the diagnosis of Pneumocystis infection should not be discarded until a careful search for the organisms using silver stains is rendered negative.     

Predictors of pneumocystosis or tuberculosis in HIV-infected Asian patients with AFB smear-negative sputum pneumonia

OBJECTIVES: To identify predictors of Pneumocystis jiroveci pneumonia (PCP) or pulmonary tuberculosis (TB) in acid-fast bacillus smear-negative HIV-infected patients and to develop clinical prediction rules. DESIGN: A cohort study conducted in consecutive hospitalized Asian patients. METHODS: Multivariate analyses were performed on the Cambodian sample to determine clinical, radiological, and biological predictors of PCP or TB at hospital admission. The Vietnamese sample was kept for independent validation. RESULTS: In Cambodia, the gold standard technique for TB and PCP were fulfilled in 172 (27 cases) and 160 (84 cases) patients, respectively. For TB, independent predictors included the following: headache [odds ratio (OR) 3.0; 95% confidence interval (CI) 1.04 to 8.6], localized radiological opacity (OR 5.8; 95% CI 1.9-17.9), and mediastinal adenopathy (OR 10.1; 95% CI 3.5 to 29.0); and for PCP: resting oxygen saturation <90% (OR 3.3; 95% CI 1.3 to 8.5 for resting arterial oxygen saturation >or=80%; and OR 9.1; 95% CI 1.8 to 44.5 for resting arterial oxygen saturation <80%), trimethoprim-sulphamethoxazole prophylaxis (OR 0.1; 95% CI 0.04 to 0.6), and diffuse radiological shadowing (OR 7.0; 95% CI 2.7 to 18.6). PCP risk predicted by a score based on these 3 factors ranged from 3% to 92% (Cambodia). When tested on Vietnamese patients (n = 69, 38 with PCP), the score maintained correct predictive ability (c-index = 0.72) but with poor calibration. CONCLUSIONS: The PCP score could provide a useful clinical tool to identify PCP among acid-fast bacillus smear-negative pneumonia and start specific therapy.     

Collagen diseases with pulmonary involvement]

Pulmonary involvement is a common feature in patients with various collagen diseases. Some types of the pulmonary involvement are resistant to currently available treatment regimens and thus considered as intractable conditions. These include acute/subacute interstitial pneumonia in dermatomyositis, pulmonary interstitial fibrosis in scleroderma, and diffuse alveolar hemorrhage. Acute/subacute interstitial pneumonia with the histology of diffuse alveolar damage (DAD) is mainly occurred in patients with amyopathic or hypomyopathic dermatomyositis who lack autoantibodies to aminoacyl tRNA synthetases. Intensive immunosuppressive treatment in the early phase of the disease may be effective for this intractable complication. Nearly one-third of patients with scleroderma have slowly progressive pulmonary interstitial fibrosis, leading to end-stage respiratory failure. Non-specific interstitial pneumonia (NSIP) with an excessive fibrotic change is a major histology of these patients. There are accumulating evidences showing the effectiveness of cyclophosphamide in patients with this intractable condition, especially those with active alveolitis. Diffuse alveolar hemorrhage is a fatal complication mainly occurred in patients with systemic lupus erythematosus and those with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, including microscopic polyangitis (MPA) and Wegener's granulomatosus. Immediate diagnosis and introduction of intensive treatment are necessary to save the patients with this complication.     

Uncommon histopathological findings in fatal measles infection: pancreatitis, sialoadenitis and thyroiditis

Aims : We report uncommon histopathological findings in fatal measles infection. Methods and results : We describe the autopsies of four patients who died during a measles outbreak in São Paulo, Brazil, in 1997. Two of the patients were children receiving chemotherapy for non‐Hodgkin's lymphoma, one was an adult with acquired immunodeficiency syndrome (AIDS) and the fourth was an apparently healthy woman. All patients had their deaths attributed to measles pneumonia. The autopsies revealed extensive giant cell pneumonia and diffuse alveolar damage, severe acute pancreatitis, necrotizing sialoadenitis and thyroiditis due to measles. Measles antigen was detected in lung tissue using a monoclonal anti‐measles antibody. Conclusions : Pancreatitis, thyroiditis and sialoadenitis are not previously reported histopathological findings in measles infection. Pancreatitis is a potentially severe complication and should be considered when treating patients with atypical measles.     

Two forms of diffuse alveolar damage in the lungs of patients with acute respiratory distress syndrome

Acute respiratory distress syndrome is a severe disease, the treatment and pathophysiology of which are not completely established. The pathology of acute respiratory distress syndrome involves diffuse alveolar damage, which comprises severe alveolar epithelial cell damage, hyaline membrane formation, and festinate myofibroblast proliferation and fibrosis in the intra-alveolar spaces. We performed a clinicopathologic investigation of 26 autopsy cases of diffuse alveolar damage. Three cases of them were diagnosed as acute interstitial pneumonia that is idiopathic illness and resembles pathologically organizing diffuse alveolar damage. Immunohistochemical staining for types I and IV collagen, α-smooth muscle actin, and Ki-67 was carried out, and the sites of myofibroblast proliferation and type I collagen production were examined. All diffuse alveolar damage cases in the proliferative phase showed intra-alveolar myofibroblast proliferation. When diffuse alveolar damage was diagnosed pathologically as being due to severe infection, all 7 patients showed multiple organ dysfunction syndrome, whereas only 2 of 7 patients showed interstitial myofibroblast proliferation. When diffuse alveolar damage was attributed to tumor treatment with chemotherapy or to drug toxicity, 3 of 16 patients showed multiple organ dysfunction syndrome; 15 of 16 showed interstitial myofibroblast proliferation, 3 of 3 acute interstitial pneumonia patients did not show multiple organ dysfunction syndrome; and 3 of 3 acute interstitial pneumonia showed marked interstitial myofibroblast proliferation. These results suggest that the pathophysiologic mechanism of diffuse alveolar damage caused by severe infection is one of systemic circulation disturbance, although the mechanism underlying diffuse alveolar damage due to tumor with chemotherapy or drug toxicity appears to involve interstitial pneumonia-like lesions that are similar to acute interstitial pneumonia.     

Pneumocystis jiroveci internal transcribed spacer types in patients colonized by the fungus and in patients with pneumocystosis from the same French geographic region

Pneumocystis jiroveci (human-derived Pneumocystis) infections can display a broad spectrum of clinical presentations, of which pulmonary colonization with the fungus may represent an important part, occurring frequently in patients with various underlying diseases and presenting alternative diagnoses of acute pneumocystosis (Pneumocystis carinii pneumonia [PCP]). There are few data concerning the P. jiroveci genotypes involved in pulmonary colonization, whereas several genotypes responsible for PCP in immunocompromised patients have been described. In this study, P. jiroveci genotypes have retrospectively been investigated and compared in 6 colonized patients and in 11 patients with PCP who were in the same hospital. Seventeen archival bronchoalveolar lavage samples were genotyped at internal-transcribed spacer 1 (ITS1) and ITS2 of the nuclear rRNA operon. Fourteen different genotypes were identified, of which 1 was found only in colonized patients, 10 were found only in patients with PCP, and 3 were found in both patient populations. Mixed infections were diagnosed in 2 of the 6 colonized patients and in 6 of the 11 patients with PCP. The results show that similar genotypes can be responsible for PCP as well as pulmonary colonization. There is a high diversity of genotypes in colonized patients and in patients with PCP. Mixed infections may occur in these two patient populations. These shared features of P. jiroveci ITS genotypes in colonized patients and patients with PCP suggest that human populations infected by P. jiroveci, whatever the clinical manifestation, may play a role as a common reservoir for the fungus.     

Pathologic pulmonary findings in children with the acquired immunodeficiency syndrome: a study of ten cases

Lung tissue and tissue from the lymphoreticular system obtained at open biopsy and/or autopsy were studied in ten children with the acquired immunodeficiency syndrome (AIDS). One or both parents of nine of the children had AIDS or risk factors for AIDS. The remaining child had hemophilia. The following pulmonary lesions were seen: 1) diffuse alveolar damage (DAD), 2) Pneumocystis carinii and/or cytomegalovirus pneumonitis, 3) lymphoid interstitial pneumonitis (LIP), and 4) desquamative interstitial pneumonitis (DIP). Combinations of such factors as mechanical ventilation, oxygen therapy, and opportunistic infection played a role in the pathogenesis of DAD. Opportunistic infections were related to the defective cell-mediated immunity in these children. The clinical, epidemiologic, immunologic, and pathologic features of the thymuses of these patients indicate that the immune deficiency was unlikely to have been of congenital origin. The immunologic abnormalities may also have been related to the pathogenesis of LIP and DIP. Neither LIP nor DIP has been described in adults with AIDS. Open lung biopsy is of practical importance in the diagnosis and treatment of pulmonary disease in children with AIDS.     

Mycobacterium kansasii diffuse pulmonary infection in a patient with acquired immune deficiency syndrome. Successful therapy with an antituberculous regimen

Mycobacterium kansasii is a rare cause of disseminated mycobacterial infection in patients with the acquired immune deficiency syndrome (AIDS). It occurs as the index AIDS diagnosis in only 0.2% of AIDS cases. Previously reported cases of AIDS-associated M. kansasii infection have manifested as diffuse interstitial pneumonitis and diffuse small bowel inflammation and have been refractory to antimycobacterial therapy. The authors now report success in treating a hypoxemic patient with AIDS-associated M. kansasii diffuse granulomatous interstitial pneumonitis that was diagnosed by open lung biopsy. The patient has no evidence of mycobacterial disease after 12 months of therapy with isoniazid, rifampin, and ethambutol.     

Terminal diffuse alveolar damage in relation to interstitial pneumonias. An autopsy study

Acute exacerbations of idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis (IPF/CFA) are rare and typically terminal events, but their relationship to underlying patterns of idiopathic interstitial pneumonias is unknown. We reviewed autopsy material from patients who died of diffuse alveolar damage in the clinical setting of pulmonary fibrosis, both idiopathic and with background fibrosing alveolitis with connective tissue disorders (FA-CTDs), and compared them with cases of acute interstitial pneumonia. Of 15 patients with acute exacerbations of IPF/CFA (n = 12) or FA-CTD (n = 3), 12 had a background pattern of usual interstitial pneumonia and 3 had fibrotic nonspecific interstitial pneumonia. All cases of fibrotic nonspecific interstitial pneumonia were seen in association with FA-CTD. The cause of acute exacerbations is unknown, but our data suggest that toxic effects of oxygen and triggering infection are unlikely causes. In patients with CTDs, it remains uncertain whether the acute exacerbation is related to the fibrosis, the associated CTD, or a combination of these factors. Acute exacerbations of IPF/CFA may be a more common terminal event than previously thought.     

Genotypes at the internal transcribed spacers of the nuclear rRNA operon of Pneumocystis jiroveci in nonimmunosuppressed infants without severe pneumonia

The frequency of Pneumocystis jiroveci (human-derived Pneumocystis) in immunocompetent infants developing acute respiratory syndromes has recently been evaluated and has been shown to be close to 25%. Until now, there have been no data on the genomic characteristics of the fungus in these patients, while molecular typing of P. jiroveci organisms was mostly performed with samples from immunosuppressed patients with pneumocystosis (Pneumocystis carinii pneumonia [PCP]). The present report describes the genotypes of P. jiroveci organisms in 26 nonimmunosuppressed infants developing a mild Pneumocystis infection contemporaneously with an episode of bronchioloalveolitis. The typing was based on sequence analysis of internal transcribed spacers (ITSs) 1 and 2 of the rRNA operon, followed by the use of two typing scores. By use of the first score, 11 P. jiroveci ITS types were identified: 10 were previously reported in immunosuppressed patients with PCP, while 1 was newly described. By use of the second score, 13 types were identified, of which 2 were newly described. The most frequent type was identified as type B(1)a(3) (first score), which corresponds to type Eg (second score). Mixed infections were diagnosed in three infants. The occurrence of such diversity of P. jiroveci ITS types, an identical main type, and mixed infections has previously been reported in immunosuppressed patients with PCP. Thus, the P. jiroveci ITS genotypes detected in immunocompetent infants and immunosuppressed patients developing different forms of Pneumocystis infection share characteristics, suggesting that both groups of individuals make up a common human reservoir for the fungus. Finally, the frequency of P. jiroveci in nonimmunosuppressed infants with acute respiratory syndromes and the genotyping results provide evidence that this infant population is an important reservoir for the fungus.     

Pulmonary cytoplasmic hyalin resembling Mallory's alcoholic hyalin in the liver

Sixty-three consecutive autopsy cases of interstitial fibrosis of the lung, 6 cases of organizing pneumonia, 14 of pneumocystis pneumonia, and 20 of acute bacterial pneumonia complicating as a terminal illness listed in our Department of Pathology during a period from 1978 to 1983 were surveyed for Mallory body-like cytoplasmic hyalins in the alveolar cells. We found the hyalins in 10 of 63 cases (15.9%) with interstitial fibrosis of the lung and one of 6 cases with organizing pneumonia. Seven of the former 10 had an associated malignancy; 3 esophageal cancers, 2 lung cancers, and 2 leukemias. Five of the seven patients received an irradiation for treatment of their malignancies, subsequently developed interstitial fibrosis of the lung. Among the remaining 3 of the 10, one showed diffuse interstitial fibrosis associated with rheumatoid arthritis and two had an idiopathic type of diffuse pulmonary fibrosis. There was only one case in which the pulmonary hyalins were found in the absence of extensive interstitial fibrosis within small organizing foci of peribronchial and subpleural location. Pulmonary hyalins showed the same conventional staining properties and ultrastructural features as Mallory's alcoholic hyalins found in the liver, but did not reveal a simultaneous association with the hepatic hyalins. Pulmonary hyalins frequently stained positively with monoclonal anti-cytokeratin antibodies, more strongly at their periphery. Pulmonary hyalins were considered to be a non-specific reaction of alveolar cells to injuries, mostly in association with the pulmonary fibrosis of any etiology but not the hepatic hyalins.     

PULMONARY CYTOPLASMIC HYALIN RESEMBLING MALLORY'S ALCOHOLIC HYALIN IN THE LIVER

Sixty-three consecutive autopsy cases of interstitial fibrosis of the lung, 6 cases of organizing pneumonia, 14 of pneumocystis pneumonia, and 20 of acute bacterial pneumonia complicating as a terminal illness listed in our Department of Pathology during a period from 1978 to 1983 were surveyed for Mallory body-like cytoplasmic hyalins in the alveolar cells. We found the hyalins in 10 of 63 cases (15.9%) with interstitial fibrosis of the lung and one of 6 cases with organizing pneumonia. Seven of the former 10 had an associated malignancy; 3 esophageal cancers, 2 lung cancers, and 2 leukemias. Five of the seven patients received an irradiation for treatment of their malignancies, subsequently developed interstitial fibrosis of the lung. Among the remaining 3 of the 10, one showed diffuse interstitial fibrosis associated with rheumatoid arthritis and two had an idiopathic type of diffuse pulmonary fibrosis. There was only one case in which the pulmonary hyalins were found in the absence of extensive interstitial fibrosis within small organizing foci of peribronchial and subpleural location. Pulmonary hyalins showed the same conventional staining properties and ultrastructural features as Mallory's alcoholic hyalins found in the liver, but did not reveal a simultaneous association with the hepatic hyalins. Pulmonary hyalins frequently stained positively with monoclonal anti-cytokeratin antibodies, more strongly at their periphery. Pulmonary hyalins were considered to be a non-specific reaction of alveolar cells to injuries, mostly in association with the pulmonary fibrosis of any etiology but not the hepatic hyalins.     

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia,organizing pneumonia,nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 ± 1.11) to UIP (23.45 ± 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.     

Acute exacerbations of fibrotic interstitial lung disease

Churg A, Wright J L & Tazelaar H D
(2011) Histopathology  58 , 525–530
Acute exacerbations of fibrotic interstitial lung disease An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre‐existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non‐specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high‐dose steroid therapy.     

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.     

Type I reactions directed against Pneumocystis carinii in AIDS patients

Type I allergy directed against Pneumocystis carinii (PC) has been investigated in 14 patients with AIDS. The Pneumocystis carinii pneumonia often shows a rapid and severe course, and type I allergy against the parasite might be a pathogenic co-factor in the interstitial lung inflammation. In twelve of the AIDS patients the clinical symptoms and course of illness indicated a PC pneumonia. The basophil histamine release test was used as a sensitive test to detect type I allergy against PC. Eight of the patients showed significant histamine release when stimulated with PC. In contrast, only two patients in the group of 12 HIV antibody-positive homosexual men and none in the control group of 13 heterosexual men released histamine. The histamine release was mediated by an immunological reaction, since the release was abolished and regained by removal from and refixation to the cell surface of the cell-bound immunoglobulins before the antigen challenge. The results suggest an involvement of type I allergy as a pathogenic co-factor in Pneumocystis carinii pneumonia.     

Organizing pneumonia and pulmonary lymphatic architecture in diffuse alveolar damage

Diffuse alveolar damage represents the pathologic basis of most cases of the acute respiratory distress syndrome. Diffuse alveolar damage reflects injury to the pulmonary alveolar wall and microvasculature, leading to the exudation of water and plasma proteins that can overwhelm the local lymphatic drainage. Organizing pneumonia is a prominent histopathologic feature in some cases of diffuse alveolar damage. We examined whether diffuse alveolar damage-organizing pneumonia and changes in lymphatic architecture might be indicators of clinical outcome in acute respiratory distress syndrome. Formalin-fixed lung sections (n = 26) from thoracoscopic lung biopsies of patients with diffuse alveolar damage in the fibroproliferative phase, with or without organizing pneumonia, were immunostained with anti-CD31 and anti-D240, markers of vascular and lymphatic endothelium, respectively, and examined by morphometric analysis. Positively staining vessels were enumerated and maximal luminal diameters recorded in randomly selected low-power fields. Patients with diffuse alveolar damage-organizing pneumonia showed greater survival than those with diffuse alveolar damage (67% versus 33%, P = .03). The maximal luminal diameter of D240+ lymphatic vessels was larger for diffuse alveolar damage-organizing pneumonia than diffuse alveolar damage (28 +/- 4 versus 59 +/- 16 microm, P = .02). In addition, larger lymphatic luminal diameters (28 +/- 4 versus 47 +/- 11 microm) were associated with increased survival (P = .12). We conclude that lung biopsy histopathology and pulmonary lymphatic morphology may predict survival in acute respiratory distress syndrome.