RESUMO
Recently, an increased frequency of thromboembolic events has been reported after the administration of anticancer drugs. The precise mechanism by which these vascular phenomena occur is unknown. The current work aims at evaluating the alterations of the coagulation and the fibrinolysis systems during the administration of antineoplastic agents by means of newly developed markers of haemostasis. This investigation comprised 25 lung cancer patients treated with multidrug combination chemotherapy. D-dimer, plasmin-alpha 2-antiplasmin complex, fibrin degradation products, fibrinogen, antithrombin III, thrombin-antithrombin III complex, prothrombin time and activated partial thromboplastin time were measured from samples taken before and on days 2, 5, 7, 14 and 21 after the administration of antineoplastic drugs. A significant reduction in plasma concentration of fibrinolytic activity markers, DD and PAP, was observed on days 5 and 7, and on days 2, 5, 7 and 14, respectively, following the administration of chemotherapeutic drugs. Statistically significant shortening of PT and APTT on days 2, 5, 7 and 14, as well as significant elevation of the thrombin generation marker TAT were observed on days 5 and 7 after chemotherapy. These results show that relatively higher levels of coagulation activation and a lower fibrinolytic activity occur during cytotoxic drug therapy compared with basal values. Small variations of haemostatic values and a short follow-up period may explain why no thrombotic events were observed during this study. Although further studies must be done to clarify these findings, the results of this investigation suggest that an imbalance of the coagulation-fibrinolysis system might be a contributing factor in the pathogenesis of thrombotic complications during chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Neoplasias Pulmonares/sangue , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Testes de Coagulação Sanguínea , Feminino , Fibrinólise/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Rheumatoid arthritis is a chronic inflammatory disease caused essentially by an immune-mediated mechanism. However, abnormalities of the clotting system have also been incriminated as having an important role in the pathogenesis of this disease. This study aims at assessing the clotting system and collagen metabolism alterations and the relationship between perturbances of the hemostatic pathway and the destructive and fibroproliferative processes in patients with rheumatoid arthritis. The coagulation system was evaluated by measuring thrombin-antithrombin III complex (TAT), prothrombin time (PT), activated partial thromboplastin time (APTT), and antithrombin III (AT-III). The fibrinolysis system was assessed by measuring fibrin degradation products (FDP), fibrinogen (FBG), alpha 2-antiplasmin (alpha 2-PI), D-dimer (DD) and plasmin-alpha 2-antiplasmin complex (PAP). As markers of collagen metabolism, the type III procollagen peptide (PIIIP) and the 7S domain of type IV collagen (7S-collagen) were determined. Blood concentrations of DD, PAP, TAT, PIIIP, and 7S-collagen were significantly higher in rheumatoid arthritis patients compared to controls. Serum levels of PIIIP were significantly correlated with PT, APTT, AT-III, FDP, and DD. 7S-collagen levels were inversely related to AT-III and FBG values. This study demonstrated the occurrence of a subclinical intravascular coagulation in rheumatoid arthritis and suggested the important role of blood coagulation in the alteration of the extracellular matrix metabolism in this disease.
Assuntos
Antifibrinolíticos , Artrite Reumatoide/sangue , Artrite Reumatoide/metabolismo , Coagulação Sanguínea/fisiologia , Colágeno/metabolismo , Adulto , Antitrombina III/metabolismo , Artrite Reumatoide/complicações , Biomarcadores , Coagulação Intravascular Disseminada/etiologia , Matriz Extracelular/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinolisina/metabolismo , Fibrinólise/fisiologia , Hemostasia/fisiologia , Humanos , Peptídeo Hidrolases/metabolismo , Pró-Colágeno/metabolismo , alfa 2-Antiplasmina/metabolismoRESUMO
Clotting abnormalities are well-recognized complications that occur with high frequency in patients suffering from underlying malignant diseases. New and highly sensitive molecular markers of hemostasis, thrombin-antithrombin III complex (TAT III), D-dimer fragments (DD), and plasmin-alpha 2-antiplasmin complex (PIC) were measured in 58 consecutive lung cancer patients. Significant elevation in the blood concentrations of DD, PIC, and TAT was found in lung cancer patients, with either extensive or limited disease compared with values obtained in a healthy control group and in another group of patients with chronic obstructive pulmonary disease. Patients with distant metastasis exhibited significantly higher levels of these parameters as compared to those without metastasis. These data indicated that there was a subclinical activation of blood coagulation and fibrinolysis in lung cancer from the early clinical stages of the disease. In addition, there appeared to be different levels of clotting activation according to histologic type of tumor and response to chemotherapy.
Assuntos
Antifibrinolíticos/sangue , Antitrombina III/análise , Biomarcadores Tumorais/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinolisina/análise , Neoplasias Pulmonares/sangue , Peptídeo Hidrolases/análise , alfa 2-Antiplasmina/análise , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/secundário , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Cisplatino/uso terapêutico , Feminino , Fibrinólise , Hemostasia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Indução de Remissão , Trombose/sangueRESUMO
The occurrence of thrombotic complications is commonly associated with poor prognosis in patients with malignancy. However, the prognostic significance of the subclinical activation of the clotting system, frequently observed in cancer patients, is unknown. The purpose of the present study was to evaluate the value of the pre-thrombotic state for predicting survival of lung cancer patients. This investigation comprised 70 lung cancer patients without clinical or laboratory diagnosis of intravascular coagulation. There were 49 cases with non-small and 21 with small cell carcinomas. Samples taken in controls were available for comparison. The clotting system was assessed measuring thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP). The independent value of these clotting markers to predict survival was evaluated in relation with previously well-established prognostic factors for lung cancer patients. Plasma concentration of each parameter was significantly higher in cancer patients as compared to that of controls. The plasma level of PAP was a predictor of survival independently from the stage of disease, sex, age, histological type, performance status, tumor size and the presence of distant metastasis. Discriminant analysis of PAP plasma concentration identified 2 groups with significant difference in survival rate in all patients, cases in advanced stages of disease and in those with small and non-small cell lung cancer. The results of the present study showed prognostic significance of the subclinical activation of the clotting system, particularly of the fibrinolytic pathway, in lung cancer. Newly developed markers of fibrinolysis might be potentially applicable for predicting outcome in malignancy.
Assuntos
Antifibrinolíticos/metabolismo , Fibrinolisina/metabolismo , Neoplasias Pulmonares/química , alfa 2-Antiplasmina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitrombina III/metabolismo , Biomarcadores Tumorais/sangue , Testes de Coagulação Sanguínea , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Pequenas/química , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peptídeo Hidrolases/metabolismo , Valor Preditivo dos Testes , PrognósticoRESUMO
Recently, many studies have reported that collagen metabolism markers, such as the aminoterminal propeptide of type IIE collagen (PIIIP) and the 7-S domain of type TV collagen (7-S collagen), increased in malignancy and that, they correlate with the clinical behavior of the disease. The objective of the present study was to assess the serum concentration of these collagen markers in relation to the clinical progression of the disease and during chemotherapy in lung cancer patients. This study comprised 48 lung cancer patients. Sixteen patients underwent cisplatin-based chemotherapy. Samples taken from controls were available for comparison. Serum concentrations of PIIIP and 7S-collagen were significantly higher as compared to the control group. While the collagen markes tended to decrease in the responder patients, they increased significantly after chemotherapy in the non-responder group. Collagen markers are suggested to be potentially useful for the early evaluation of the tumor response to chemotherapy in lung cancer.
RESUMO
The Beaudette 42 strain of avian infectious bronchitis virus, Sato strain of Newcastle disease virus, and Uchida strain of avian reovirus were passaged in Chinese hamster lung cells (Don), and some properties were examined. The Don-passaged strains showed a difference in replication in Don and chicken embryo kidney cells in one-step growth curve examinations and a partial modification in pathogenicity to chicken embryos; nevertheless, neutralization tests revealed no serological alteration.
Assuntos
Embrião de Galinha/microbiologia , Coronaviridae/patogenicidade , Vírus da Bronquite Infecciosa/patogenicidade , Vírus da Doença de Newcastle/patogenicidade , Reoviridae/patogenicidade , Animais , Linhagem Celular , Cricetinae , Vírus da Bronquite Infecciosa/crescimento & desenvolvimento , Rim , Vírus da Doença de Newcastle/crescimento & desenvolvimento , Reoviridae/crescimento & desenvolvimentoRESUMO
Eight etiologic agents isolated from field cases in Japan were identified as isolates of infectious bronchitis virus by agar-gel diffusion, buoyant-density determination on sucrose-density centrifugation, and morphological study by electron microscope of the purified viruses. In studies of the antigenic relationships of the eight isolates and six known infectious bronchitis viruses, antigenic diversity of these viruses was recognized from the degrees of relatedness using a plaque reduction in the "constant-virus decreasing-serum" method.
Assuntos
Galinhas , Infecções por Coronaviridae/veterinária , Coronaviridae/classificação , Vírus da Bronquite Infecciosa/classificação , Doenças das Aves Domésticas/microbiologia , Animais , Antígenos Virais/análise , Infecções por Coronaviridae/microbiologia , Epitopos , Imunodifusão/veterinária , Vírus da Bronquite Infecciosa/ultraestrutura , Japão , Testes de NeutralizaçãoRESUMO
Two cases of ulcerative colitis are described: a 33-year-old woman who developed widespread bronchiectasis 7 months after undergoing colectomy, and a 72-year-old man whose colonic disease began coincidentally with the appearance of diffuse interstitial pulmonary infiltrates. In both cases, clinical correlation and common patterns of response of lung and bowel diseases suggested that the co-existence of these two pathologies might not be merely a casual relation.
Assuntos
Bronquiectasia/complicações , Colite Ulcerativa/complicações , Pneumopatias Obstrutivas/complicações , Adulto , Idoso , Feminino , Humanos , MasculinoRESUMO
The incidence of pulmonary tuberculosis in Japan has decreased remarkably. However, high frequency of tuberculosis can still be noticed in those subjects with underlying diseases, the so-called compromised host. This study aimed at to clarify the clinical characteristics of pulmonary tuberculosis in the compromised host. To achieve our objective we compare the clinical and radiological findings in patients with and without underlying disease. This study comprised 44 pulmonary tuberculosis patients. Among these, 24 cases (55%) of tuberculosis occurred in those with a pre-existing disease. Most patients of the compromised host group were seen because of pulmonary symptomatology. There were 3 cases (15%) with cavitated pulmonary infiltration in the normal host group, whereas in the compromised host group 7 cases (29%) presented cavitary lesions. From these results, it was confirmed the high frequency of pulmonary tuberculosis in patients with an underlying disease. In addition, this work suggests that the presence of an atypical radiological findings should orient the clinician to start an early work-up for the diagnosis of pulmonary tuberculosis in those high risk group of patients.
Assuntos
Tuberculose Pulmonar , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico por imagemRESUMO
Eleven inoperable patients with non-small cell lung cancer were treated as a maintenance therapy with oral etoposide 25 mg daily. The toxicity appeared during the chemotherapy were assessed in all cases, but the blood concentration of the drug were measured in 5 cases on the first and the seventh day of treatment. While the peak plasma level (Cmax) was 0.92 +/- 0.43 microgram/ml on the first day and 1.02 +/- 0.30 micrograms/ml on the seventh day of chemotherapy, AUC was 12.3 +/- 5.41 micrograms.hr/ml and 11.9 +/- 4.52 micrograms.hr/ml on the first and the seventh day, respectively. Cumulative effect of the drug did not exist, since in any of these two measurements there was no significant statistical difference between values obtained on the first and on the seventh day. Regarding the toxicity of the drug, bone marrow suppression with abnormal reduction of peripheral white blood cells was observed. Though grade 2 adverse reaction was found in 6 cases, stopping drug administration for 2 weeks, enabled to re-administer the drug. Alopecia and liver or renal injury were not observed, and in spite of the presence of nausea and anorexia in one case, maintenance therapy could continue in all cases. Based on these results we concluded that etoposide can be safely administered as a maintenance therapy on out-patient basis.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Etoposídeo/farmacocinética , Neoplasias Pulmonares/metabolismo , Administração Oral , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/efeitos dos fármacosAssuntos
Colágeno/sangue , Neoplasias Pulmonares/sangue , Ativação de Neutrófilo , alfa 1-Antitripsina/análise , Adenocarcinoma/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Progressão da Doença , Humanos , Elastase Pancreática , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangueRESUMO
Collagen disease are chronic multisystemic disorders affecting many organs. Pulmonary involvement is frequently associated with these collagen diseases. The usefulness of the diffusion capacity of the lung for the early detection of pulmonary involvement was assessed in 182 collagen vascular disease patients. In addition, the clinical characteristics of those patients with pulmonary lesions were also evaluated. Among these, there were 69 cases of chronic rheumatoid arthritis (RA), 39 progressive systemic sclerosis (PSS), 24 systemic lupus erythematosus (SLE), 12 dermatomyositis-polymyositis (DM-PM), 12 mixed connective tissue disease (MCTD), 11 Sjögren syndrome (SS), 9 Behçet's disease (BD) and 6 unclassified connective tissue disease (UCTD). Patients with normal chest X-ray but with pulmonary dysfunction were recognized in 56% of RA, 59% of PSS, 50% of SLE, 50% of DM-PM, 71% of MCTD, 33% of SS, and 50% of BD cases. Moreover, a higher degree of immunological abnormalities was observed in those with pulmonary complications. From these results, we conclude that diffusion lung capacity is a useful index for the early diagnosis of pulmonary involvement in collagen vascular disorders.
Assuntos
Doenças do Colágeno/complicações , Pneumopatias/diagnóstico , Capacidade de Difusão Pulmonar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Colágeno/fisiopatologia , Feminino , Humanos , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
We evaluated the frequency and the backgrounds of lung cancer patients with obstructive pneumonitis. Among 84 cases of lung cancer, 35 presented with bronchial obstruction at bronchoscopy or on radiological studies. Of these 35 cases, 8 had infectious obstructive pneumonitis. This complication was observed more commonly in patients with squamous cell carcinoma. A comparative analysis of the immunological and nutritional states before the occurrence of bacterial complication was performed on patients with infectious obstructive pneumonitis and those with non-infectious obstructive pneumonitis. The serum concentration of total protein, albumin and total cholesterol was significantly lower in patients who subsequently developed bronchial obstruction and bacterial infection, compared to concentrations in patients with non-infectious obstructive pneumonitis. Similarly, there was significant decrease in the number of peripheral lymphocytes, and neutrophils as well as a significant reduction of the serum concentration of IgM in the group of patients with infectious complications. These results suggest that nutritional and immunological deficiencies, in association with local airway obstruction, may be determining factors in the occurrence of infectious obstructive pneumonitis in patients with lung cancer.
Assuntos
Neoplasias Pulmonares/complicações , Pneumonia/etiologia , Idoso , Infecções Bacterianas , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/imunologia , Feminino , Humanos , Imunoglobulina M/sangue , Contagem de Leucócitos , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Pneumonia/imunologia , Pneumonia/microbiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Coagulopathies often are associated with malignant tumors. The pathogenesis of these complications in cancer is not clear. Host inflammatory (monocyte/macrophage) cell-mediated triggering of clotting activation has been suggested. METHODS: The objective of this study was to evaluate the role of neutrophil-derived elastase in the activation of blood coagulation and fibrinolysis in lung cancer. The study population was 42 consecutive patients with lung cancer (34 men and 8 women). Thirteen patients had small cell lung cancer (SCLC), 13 had squamous cell lung cancer, and 16 had adenocarcinoma. Hemostatic function was assessed by measuring D-dimer (DD), thrombin-antithrombin III complex (TAT), plasmin-alpha 2-antiplasmin complex (PAP), fibrin degradation product (FDP), fibrinogen, prothrombin time (PT) and activated partial thromboplastin time (APTT). Elastase-alpha 1-protease inhibitor (EPI) complex was measured as a marker of neutrophil activation. RESULTS: Significant elevation of the elastase plasma levels and coagulation-fibrinolysis parameters was found in patients with cancer compared with control subjects. Among all patients, the plasma concentration of EPI was significantly correlated with APTT, DD, TAT, PAP, and fibrinogen. Although in patients with non-small cell lung cancer (non-SCLC), DD, TAT, PAP, APTT, and fibrinogen were significantly correlated with EPI, such a correlation was not found in patients with SCLC. Patients with non-SCLC had stronger correlation of EPI with TAT, PAP, and PT than did patients with advanced stages of disease. CONCLUSION: The activation of coagulation-fibrinolysis system in lung cancer may be triggered, at least in part, by an increased release of neutrophil elastase. This mechanism is stage related and seems to operate predominantly in non-SCLC.
Assuntos
Antifibrinolíticos , Coagulação Sanguínea/fisiologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Pequenas/sangue , Granulócitos/enzimologia , Neoplasias Pulmonares/sangue , Elastase Pancreática/sangue , Adenocarcinoma/sangue , Adenocarcinoma/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitrombina III/análise , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma de Células Pequenas/enzimologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/enzimologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Fibrinolisina/análise , Fibrinólise/fisiologia , Humanos , Elastase de Leucócito , Neoplasias Pulmonares/enzimologia , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Peptídeo Hidrolases/análise , Tempo de Protrombina , alfa 2-Antiplasmina/análiseRESUMO
BACKGROUND: Evidence suggests that the fibrinolysis system and peritumoral connective tissue play important roles in tumor spread. METHODS: In this study, the authors evaluated the following parameters in 30 consecutive patients with lung cancer: thrombin-antithrombin complex (TAT), cross-linked fibrin split products D-dimer (DD), plasmin-alpha 2-antiplasmin inhibitor complex (PAP), and two antigens related to connective tissue, the aminoterminal propeptide of type III procollagen (PIIIP) and the 7S domain of type IV collagen (7S-collagen). RESULTS: Each parameter was increased significantly in the patients with cancer compared with the control subjects. Except for PIIIP, their concentration in blood was elevated to a significantly greater extent in the patients with distant metastases. The PAP concentration correlated well with the plasma concentration of TAT (r = 0.5; P < 0.01) and DD (r = 0.9; P < 0.0001). There was also a strong correlation between the serum concentrations of PIIIP and 7S-collagen (r = 0.7; P < 0.001). In patients with localized disease, DD levels were correlated significantly with those of PIIIP (Spearman rank-order correlation [rs] = 0.6; P < 0.025) and 7S-collagen (rs = 0.6; P < 0.01). In the group with disseminated metastases, there was a significant inverse relationship between serum PAP concentrations and serum concentrations of 7S-collagen (rs = -0.6; P < 0.025). CONCLUSIONS: These results confirm the presence of a subclinical chronic activation of the parameters of intravascular clotting-fibrinolysis and alterations in the extracellular matrix of patients with lung cancer. These parameters may be useful as indicators of the clinical progression of malignant disease, particularly of lung cancer.
Assuntos
Coagulação Sanguínea , Colágeno/metabolismo , Fibrinólise , Neoplasias Pulmonares/fisiopatologia , Adulto , Idoso , Análise de Variância , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
We studied the effect of inhalation of various concentrations of nitric oxide (NO)(2 ppm, 5 ppm, and 10 ppm) on the pulmonary circulation and on arterial oxygenation in 11 patients with stable chronic obstructive pulmonary disease. Inhalation of 2 ppm of NO resulted in values of mean pulmonary arterial pressure significantly lower than those measured while breathing room air only (24.1 +/- 1.7 vs 20.7 +/- 1.7 mmHg, p < 0.00001). The decrease in pulmonary artery pressure associated with inhalation of 2 ppm NO was only slightly less than the decrease associated with 10 ppm; the difference between the two was not considered to be clinically relevant. The pulmonary vascular resistance was significantly lower during inhalation of 2 ppm NO than during inhalation of room air only (495 +/- 40 vs 382 +/- 34 dyne.sec/cm5, p < 0.00001); the effects of inhaling 2 ppm and 10 ppm did not differ significantly. the partial pressure of oxygen in arterial blood was significantly lower after inhalation of 2 ppm NO than of baseline (61.1 +/- 2.3 vs 57.6 +/- 2.2 mmHg, p < 0.01). These results show that inhalation of NO worsens arterial oxygenation in patients with chronic obstructive pulmonary disease.
Assuntos
Pneumopatias Obstrutivas/tratamento farmacológico , Pneumopatias Obstrutivas/fisiopatologia , Óxido Nítrico/administração & dosagem , Administração por Inalação , Idoso , Humanos , Hipertensão Pulmonar/complicações , Masculino , Oxigênio/sangue , Pressão Parcial , Circulação Pulmonar/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacosRESUMO
Inhaled nitric oxide (NO) has been shown to reduce the mean pulmonary artery pressure (mPAP) and to improve PaO2 in patients with acute respiratory failure undergoing oxygen (O2) therapy. However, inhaled NO reduced pulmonary hypertension without improving PaO2 in patients with chronic obstructive pulmonary disease (COPD). This study was intended to compare the hemodynamic and gas exchange responses during inhalation of NO or O2 with those observed during the combined inhalation of NO and O2 in 10 spontaneously breathing COPD patients. Hemodynamic and blood gas parameters were measured after breathing: (1) room air; (2) NO added to room air; (3) O2 (1 L/min); or (4) NO and O2. During inhalation of 2 ppm NO added to room air, the mPAP (23.1 +/- 2.5 versus 20.6 +/- 2.2 mm Hg) and the pulmonary vascular resistance (PVR) (434 +/- 70 versus 378 +/- 50 dyne s/cm5) were significantly (p < 0.05) lower than those measured with room air. However, the values of PaO2 did not improve. The combined inhalation of NO and O2 was associated not only with a significant (p < 0.05) decrease of mPAP (21.4 +/- 2.3 versus 19.7 +/- 1.8 mm Hg) and PVR (431 +/- 72 versus 370 +/- 44 dyne s/cm5), but also with a remarkable improvement (p < 0.05) in the values of PaO2 (91.4 +/- 6.6 versus 111.5 +/- 7.8 mm Hg) as compared with values obtained during the inhalation of O2 alone. These findings suggest that combined therapy with NO and O2 may constitute an alternative approach to treating patients with COPD and pulmonary hypertension.