Effect on dyspnoea and hypoxaemia of inhaled N(G)-nitro-L-arginine methyl ester in hepatopulmonary syndrome.

Hepatopulmonary syndrome--a complication of chronic liver disease-is characterised by hypoxaemia, which results from widespread intrapulmonary vascular dilatations. Amplified production of pulmonary nitric oxide is thought to be important in development of this disorder in patients with liver cirrhosis. Here, we report a 64-year-old man with hepatopulmonary syndrome associated with hepatitis-C-virus-related cirrhosis. We gave the patient nebulised N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, which enhanced oxygenation (arterial oxygen pressure increased from 6.98 to 9.45 kPa). After L-NAME, the distance the patient could walk in 6 min rose by 92 m. Administration of L-NAME by aerosol might offer a new approach to treatment of hepatopulmonary syndrome.

Exhaled nitric oxide in systemic sclerosis: relationships with lung involvement and pulmonary hypertension.

OBJECTIVE: To measure nitric oxide (NO) concentration in exhaled air of patients with systemic sclerosis (SSc) and to investigate its relationships with lung involvement, complicated or not by pulmonary hypertension (PH). METHODS: Exhaled NO was measured by chemiluminescence in 47 patients with SSc (16 with PH) and in 30 controls. All the patients underwent Doppler echocardiography to assess pulmonary artery pressure (PAP), lung function tests, and thin section computed tomographic scans of the lung to quantify the extent of fibrosing alveolitis. RESULTS: Exhaled NO levels were higher in patients with SSc (16.6 +/- 9.1 ppb), particularly those with interstitial lung disease (ILD) (18.3 +/- 10.4 ppb), compared to controls (9.9 +/- 2.9 ppb; p < 0.0001). In patients with PH, exhaled NO was less than in patients without PH (10.7 +/- 5.9 vs 19.6 +/- 9 ppb, respectively; p < 0.001), and patients with PH without ILD had even lower exhaled NO than patients with PH and ILD (6.6 +/- 1.1 vs 12.6 +/- 6.3 ppb; p = 0.004). There was an inverse correlation between PAP and exhaled NO (r = 04).53, p = 0.004). Exhaled NO was not correlated to age, disease duration, current therapy, or form of disease (limited or diffuse). CONCLUSION: The increased concentration of exhaled NO in patients with SSc may reflect respiratory tract inflammation. The relatively low value of exhaled NO in patients with PH and the negative correlation between PAP and exhaled NO suggest the important role of NO in regulating pulmonary vascular resistance in patients with SSc.

Exhaled nitric oxide and impaired oxygenation in cirrhotic patients before and after liver transplantation.

BACKGROUND: Nitric oxide may be involved in the impaired oxygenation of cirrhotic patients, a condition that improves in most patients after liver transplantation. OBJECTIVE: To compare oxygenation and nitric oxide concentrations before and after liver transplantation. DESIGN: Before-and-after observational study. SETTING: Academic medical center. PATIENTS: 18 patients with cirrhosis and no obvious cardiopulmonary disease who underwent successful orthotopic liver transplantation. INTERVENTION: Orthotopic liver transplantation. MEASUREMENTS: Blood gas analysis, measurement of exhaled nitric oxide, contrast-enhanced echocardiography, and pulmonary function tests. RESULTS: Before transplantation, the mean (+/- SD) exhaled nitric oxide concentration was higher in patients than in normal controls (13 +/- 4.9 parts per billion [ppb] compared with 5.75 +/- 1.9 ppb; P < 0.001). After transplantation, the alveolar-arterial oxygen gradient significantly decreased (from 17.3 +/- 7.1 mm Hg to 9 +/- 5.2 mm Hg; P < 0.001), as did the exhaled nitric oxide concentration (from 13 +/- 4.9 ppb to 6.2 +/- 2.8 ppb; P < 0.001). The decrease in the exhaled nitric oxide concentration was significantly correlated with the decrease in the alveolar-arterial oxygen gradient (r = 0.56; P = 0.014). Five patients met the criteria for the diagnosis of the hepatopulmonary syndrome before transplantation; the syndrome was cured by transplantation. CONCLUSIONS: The correlation between the decrease in exhaled nitric oxide concentration after liver transplantation and the improvement in oxygenation reinforces the hypothesis that nitric oxide is an important mediator of impaired oxygenation in patients with cirrhosis.

Exhaled nitric oxide and oxygenation abnormalities in hepatic cirrhosis.

Impaired arterial oxygenation, ranging from increased alveolar-arterial oxygen gradient (AaDo2) to hypoxemia, is commonly present in patients with cirrhosis. Nitric oxide (NO), through pulmonary vasodilatation, may play a major role in the oxygen abnormalities of cirrhosis. Our aim was to study the relationship between NO production and O2 abnormalities in 45 nonsmoking patients with cirrhosis and without major cardiovascular and respiratory diseases. Intrapulmonary shunting was detected by contrast-enhanced (CE) echocardiography. Lung volumes and diffusion, arterial blood gas analysis, serum NO2-/NO3-, NO output in the exhaled air, and cardiac index by the echocardiographic method were determined in all patients. Twenty-seven (60%) patients had an abnormally increased (> 15 mm Hg) AaDo2. The mean values of exhaled NO output and serum NO2-/NO3- were significantly higher in cirrhotic patients than in controls (252 +/- 117 vs. 75.2 +/- 19 nL/min/m2, P < .0001; and 47.5 +/- 29.4 vs. 32.9 +/- 10.1 micromol/L, P < .02, respectively). In all patients, there was a significant correlation between exhaled NO and AaDo2 (r = .78, P < .0001). Twelve patients (26.6%) were found to have CE-echocardiographic evidence of intrapulmonary shunting (positive CE-echo). Nine patients were considered to have hepatopulmonary syndrome (HPS) on the basis of an AaDo2 > 15 mm Hg and positive CE-echo. These 9 patients had a mean value of exhaled NO significantly higher than patients without HPS (331 +/- 73.2 vs. 223 +/- 118.4 nL/min/m2, P < .05). In all patients, cardiac index was positively correlated with exhaled NO (r = .47, P < .001) and with serum NO2-/NO3- (r = .43, P < .01). The results suggest an important role of NO in the oxygenation and circulatory abnormalities of patients with cirrhosis.

Damage of the pharyngeal mucosa and hyperresponsiveness of airway in sinusitis.

BACKGROUND: In sinusitis bronchoconstriction is supposed to originate from pharyngobronchial reflexes triggered by seeding of the inflammatory process into the pharynx. OBJECTIVE: Our aim was to evaluate whether in sinusitis bronchial and extrathoracic airway (EA) dysfunction correlate with morphologic abnormalities of the pharyngeal mucosa. METHODS: We performed histamine inhalation challenge, nasal lavage, and nasopharyngeal biopsies in 24 nonasthmatic patients with exacerbation of chronic sinusitis. The histamine PC20 was the threshold of bronchial responsiveness, and that causing 25% fall in maximal midinspiratory flow was the threshold of EA responsiveness (PC25MIF50). Thresholds of 8 mg/ml or less were assumed to indicate bronchial hyperresponsiveness (BHR) or EA hyperresponsiveness (EAHR). PC20 and PC25MIF50 values were related to clinical data, nasal lavage fluid eosinophils, pharyngeal epithelium and basement membrane thickness, and density of submucosal vessels and nervous fibers. RESULTS: The PC20 was closely related to PC25MIF50 (p = 0.0004). Ten patients had EAHR, 9 had combined EAHR and BHR, and 5 had neither EAHR nor BHR. EAHR was strongly associated with epithelial thinning, and BHR with long-standing sinusitis, a lower PC25MIF50, increased submucosal nerve density and increased nasal lavage fluid eosinophils. CONCLUSIONS: Our findings suggest that in nonasthmatic patients with sinusitis, pharyngeal damage may contribute to airway dysfunction by favoring the access of irritants to submucosal nerve endings, with activation of constrictive reflexes to the EA. Proliferation of sensory neurons, consequent to long-lasting pharyngeal inflammation, may cause more severe EA narrowing and activate pharyngobronchial reflexes.

Systemic arterial air embolism and tension pneumothorax: two complications of transthoracic percutaneous thin-needle biopsy in the same patient.

Systemic arterial air embolism and tension pneumothorax are two rare and severe complications of transthoracic fine-needle biopsy. We report on a patient who developed both complications during the same procedure and recovered successfully after resuscitation and hyperbaric oxygen therapy. Favourable outcome of systemic air arterial embolism has been reported infrequently in the literature. In our case tension pneumothorax may have influenced favourably the course of the illness due to collapse of distal airways and the reduction of the venous return to the heart from the affected side.

Clinical utility of tissue polypeptide antigen determination in lung cancer management.

In view of the fact that pulmonary malignancies still represent an important cause of tumor death and that the high rate of unsuccessful treatment may be partly due to the late clinical presentation, efforts should be spent not only to develop new and effective treatments but also to improve early diagnosis and to identify prognostic factors and parameters useful for the monitoring of the treatment. Tumor markers, if used properly, can provide a useful support for the management of patients suffering from various malignancies, including lung cancer patients. The clinical significance of one of the most widely used tumor markers, Tissue Polypeptide Antigen (TPA), has been reviewed and showed this marker to be useful to the clinician for the management of patients with pulmonary malignancy, as a complementary tool for diagnosing and staging the tumor as well as for monitoring treatment response or relapse occurrence.

Extrathoracic and intrathoracic airway responsiveness in sinusitis.

BACKGROUND: Asthma associated with sinusitis is supposed to be sustained by bronchoconstrictive reflexes originating in extrathoracic airway (EA) receptors. OBJECTIVE: The study was designed to evaluate the relationship between EA responsiveness and bronchial responsiveness in sinusitis. METHODS: We performed histamine inhalation challenge in 106 patients with chronic sinusitis, during disease exacerbation and after treatment with antimicrobials and nasal flunisolide (100 micrograms daily) for 2 weeks. Forced expiratory volume in 1 second (FEV1) and maximal mid-inspiratory flow (MIF50) were the respective indexes of bronchial and EA narrowing; the histamine concentrations causing a 20% fall in FEV1 (PC20) and 25% drop in MIF50 (PC25MIF50) were used as thresholds of bronchial and EA responsiveness. Thresholds of 8 mg/ml or less were assumed to indicate bronchial hyperresponsiveness (B-HR) or EA hyperresponsiveness (EA-HR). RESULTS: During sinusitis exacerbation 76 patients had EA-HR, which in 46 was associated with B-HR. The values of PC20 were closely related with those of PC25MIF50 (p < 0.001). EA-HR and B-HR were strongly associated with pharyngitis. After treatment, mean PC25MIF50 and PC20 were significantly increased (p < 0.001). The improvement of PC25MIF50 was closely related to that of PC20 (p < 0.001) and to the decrease in neutrophils in nasal lavage (p < 0.05). EA-HR reversed in 58 patients and improved in 10; B-HR reversed in 29 and improved in 12. CONCLUSIONS: Our findings suggest that in sinusitis, B-HR may be sustained by constrictive reflexes originating in pharyngeal receptors, made hypersensitive by seeding of the inflammatory process.

Pulmonary lymphangioleiomyomatosis in postmenopausal women: report of two cases and review of the literature.

Pulmonary lymphangioleiomyomatosis, a disease largely confined to women in their reproductive years, is reported in two postmenopausal patients. Nine similar cases in the literature are reviewed. In older women, the disease appears to be similar to that described in younger women, with the possible exception that the clinical course may be longer and more benign after the menopause. It would appear that hormonal factors play a role in the development of the disease both before and after the menopause, and that hormonal treatment may be beneficial in the older women.

Disappearance curves of tumor markers after radical surgery.

CEA serum levels were sampled from 15 patients with lung carcinoma, 12 patients with colon carcinoma, and 5 patients with gastric carcinoma before and after radical excision of the malignancy. In addition, TPA serum levels were measured in 7 patients with lung carcinoma and CA 19.9 serum levels in 9 patients with colon carcinoma, before and after curative surgery. Irrespective of the primary malignancy, a CEA half-life of approximately 3 days was calculated. The normalization time was related to the preoperative level of the marker, being longer when the preoperative CEA level was > 20 ng/ml. The TPA half-life was slightly longer than 1 day, ranging from less than 1 day to more than 3 days, with a normalization time of about 20 days. The CA 19.9 half-life was slightly longer than 1 day with variations from less than 1 day to about 3 days. Many factors, especially associated inflammatory processes and hepatic clearance imbalances, may influence marker kinetics in the postoperative period. A correct evaluation of the clinical significance of tumor marker half-life after radical surgery will require a larger number of patients as well as careful and prolonged follow-up.

Postoperative bronchopleural fistula: endoscopic closure in 12 patients.

Twelve consecutive patients with postresectional bronchopleural fistula were treated with endoscopic application of tissue glue adhesive (methyl-2-cyanoacrylate). Eight patients had associated empyema. Endoscopic gluing was successfully accomplished in 10 cases (success rate of 83%). The two failures both had fistulas of 0.5 cm or larger. Bronchopleural fistulas developed in 8 patients early after the intervention (< 15 days): of the 4 patients without associated empyema, 3 had their fistula definitely closed after endoscopic treatment. Similarly, 3 of the 4 patients with early bronchopleural fistulas and empyema were cured after endoscopic closure of the fistula and appropriate management of the empyema. Four bronchopleural fistulas occurred late after the operation (> 15 days) and all had associated empyema. Successful endoscopic closure of the fistula was accomplished in all. Resolution of the empyema occurred in 1. We conclude that endoscopic application of tissue adhesive may be a valid therapeutic measure in selected patients with postresectional bronchopleural fistula. In late bronchopleural fistula with empyema, the closure of the fistula can be achieved, but empyema may persist and require additional surgical procedures.

[Iatrogenic esophago-tracheal fistula treated with endoscopically administered fibrin glue]. / Fistola esofago-tracheale iatrogena trattata con colla di fibrina per via endoscopica.

Successful closure of a iatrogenic tracheoesophageal fistula by means of bronchoscopic application of fibrin glue in a 77-year old patient is reported. The fistula was completely obliterated after a single application of the glue, with resolution of the clinical and radiological signs. The procedure may be suggested as an alternative to surgery or as first attempt before surgery in very selected patients with TEF.

Development of a high-performance liquid chromatographic-mass spectrometric technique, with an ionspray interface, for the determination of platelet-activating factor (PAF) and lyso-PAF in biological samples.

An HPLC-mass spectrometric technique with an ionspray interface was developed for the determination of platelet-activating factor (PAF) and PAF-related compounds in biological samples. HPLC separations were performed using a reversed-phase column. The mass spectra showed intense [M + H]+ ions. Collision-induced dissociation of protonated molecular ions gave characteristic daughter ions corresponding to the phosphorylcholine group. By selective-ion monitoring, a detection limit of 0.3 ng was obtained for all molecules; by multiple reaction monitoring, the same sensitivity was achieved for PAF whereas for lyso-PAF the limit was 3 ng. Finally, PAF was comparatively determined by bioassay and HPLC-MS after extraction from the cell pellets and the supernatants of human polymorphonuclear neutrophils unstimulated or stimulated with opsonized zymosan. The good correlation observed between these techniques indicated the reliability of HPLC-MS for biochemical studies on PAF and PAF-related molecules.

Bal T lymphocyte subsets are reduced in primary lung neoplasias.

Direct observation with an optic fibre bronchoscope facilitates the diagnosis, staging and treatment of both neoplastic and other lung diseases, and the varying diameters available enable IVth or even Vth-order bronchi to be examined. The technique can be employed for deep lung lavage or bronchoalveolar lavage (BAL) and for transbronchial biopsy. The BAL fluid, too, can be used to study lung cells and soluble components. In this study, 21 patients aged 32-79 (mean 55.5), namely 16 with lung cancer and with non-neoplastic lung diseases, were subjected to BAL to allow a study to be made of the BAL fluid cell composition. In the neoplastic group, CD3 lymphocytes were 41.3% compared with 63.2% in the peripheral blood. CD4 (24.6% vs 40.6%) and CD8 (16.6% vs 28.7%) displayed the same pattern. The CD4/CD8 ratio, on the other hand, was much the same in both groups: 1.7 vs 1.5. CD19 were higher in the BAL fluid (20.1%) than in the peripheral blood (4.8%). In the non-neoplastic group the differences between the BAL fluid and the peripheral blood are of the same sign, but less marked. In conclusion, the BAL fluid subset composition in primary lung neoplasia differs from that in the peripheral blood through a reduction of CD3, CD4 and CD8 and an increase in CD19 compared with the peripheral blood. These modifications are less evident in patients with non-neoplastic lung diseases.

Respiratory symptoms, lung function tests, airway responsiveness, and bronchoalveolar lymphocyte subsets in B-chronic lymphocytic leukemia.

A respiratory questionnaire was completed and spirometry, tests for lung volumes, diffusion capacity for CO, and methacholine bronchial challenge were performed in 24 outpatients with B-chronic lymphocytic leukemia (B-CLL), aged 44-79, presenting in different stages of their disease. In 10 patients, bronchoalveolar lavage (BAL) fluid was also obtained. Ten of twenty-four patients had symptoms consistent with chronic bronchitis, unrelated both to smoking history and to the clinical stage. Abnormal values (< 2 SD) were found in 4 patients for total lung capacity (TLC), in 9 for vital capacity (VC), 8 for forced expiratory volume in 1 sec (FEV1), 11 for MEF50, 15 for MEF25 and in 7 for diffusing capacity for carbon monoxide. Seven of nineteen patients had PD20FEV1 at less than 1,600 micrograms of methacholine chloride. There was a significantly negative correlation between white blood cell count and VC (r = 0.41, P < 0.05). A positive correlation was found between PD20FEV1 and FEV1/VC (r = 0.61, P < 0.01). The mean and SEM for BAL cells/ml was 463 (71.8) x 10(3). No leukemic cells but a marked increase in T lymphocytes (32.5 +/- 7.8%) were found in BAL fluid. There were significantly negative correlations between the number of BAL CD3+ T lymphocytes and PD20FEV1 (r = 0.61, P < 0.05), and between the number of BAL CD8+ T lymphocytes and PD20FEV1 (r = 0.84, P < 0.01). In conclusion, patients with B-CLL have a high prevalence of respiratory symptoms, small airway dysfunction and CD8 "alveolitis" related to airway responsiveness; despite the well-known lung interstitial lymphocyte infiltration in B-CLL, leukemic cells are not found in BAL fluid.

Platelet-activating factor in bronchoalveolar lavage from patients with sarcoidosis.

Platelet-activating factor (PAF), a lipid mediator of inflammation and anaphylaxis, may play a role in several physiopathologic alterations of the lung. A lipid compound with physicochemical and biologic characteristics similar to synthetic PAF was extracted and purified from bronchoalveolar lavage (BAL) fluid of 15 of 34 patients with sarcoidosis. PAF was quantitated by a bioassay on washed rabbit platelets. The specificity of platelet aggregation was assessed by using two different PAF receptor antagonists. The incidence of detectable amounts of PAF in BAL fluid of sarcoid patients was statistically significant (chi 2 = 4.064, p = 0.044) when compared with the 14 normal control subjects. The results demonstrated an increased production of PAF in the lower respiratory tract of patients with sarcoidosis. The presence of PAF in BAL fluid, however, did not correlate with radiologic stage, intensity of alveolitis, gallium scanning positivity, angiotensin-converting enzyme serum level, or lung function tests. Therefore, a direct relationship between presence of PAF in BAL fluid and activity of lung disease in patients with sarcoidosis was not directly established.

Pulmonary function in patients with pleural effusion of varying magnitude and fibrothorax.

Pulmonary function was studied in sixty patients with pleural effusion and seventy patients with fibrothorax. The patients with pleural effusion were divided into three groups according to the extent of the effusion. The patients were submitted to spirometry and arterial blood gas analysis. The effects of pleural effusion on pulmonary function is evaluated with regards to the size of effusion. Small-size pleural effusion little affects arterial oxygen tension. Pleural effusion and fibrothorax have a similar pattern of pulmonary function.

Histamine hyperresponsiveness of the extrathoracic airway in patients with asthmatic symptoms.

Functional abnormalities of the extrathoracic airway (EA) may produce symptoms mimicking bronchial asthma. We assessed the bronchial (B) and EA responsiveness to inhaled histamine in 40 patients with asthmatic symptoms and in nine asymptomatic controls. FEV1 and maximal mid-inspiratory flow (MIF50) were used as index of bronchial and EA narrowing. Hyperresponsiveness of the intra-(BHR) or extra-(EA-HR) thoracic airway was diagnosed when the provocative concentrations of histamine (PC20FEV1 or PC25MIF50) were less than 8 mg/ml. Fiberoptic laryngoscopy was performed in nine patients and three controls. The glottal region was measured at mid-volume of maximal inspiration (AgMI) and expiration (AgME) before and after histamine. Predominant EA-HR was found in 13 patients, predominant BHR in 12, equivalent BHR and EA-HR in another 12; no significant airway narrowing was observed in three patients and in the nine controls. EA-HR was significantly associated with female sex, sinusitis, post-nasal drip, dysphonia; BHR with atopy, wheezing and lower MEF50. The percent change in AgMI after histamine was closely related to the PC25MIF50 (r = 0.87, P less than 0.001), that of AgME to the PC20FEV1 (r = 0.78, P less than 0.01). These findings suggest that the assessment of EA responsiveness may be useful in the evaluation of asthmatic symptoms, especially in patients with no BHR.