Replication-deficient adenovirus induces expression of interleukin-8 by airway epithelial cells in vitro.

Preclinical studies with first-generation adenovirus (Ad) vectors administered in vivo to the respiratory tract have demonstrated a nonspecific host response consisting, in part, of parenchymal neutrophil accumulation followed by mononuclear cell and macrophage accumulation. We hypothesized that the mechanism for this host response might be the elaboration of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from the airway epithelium following the exposure to Ad. To evaluate this hypothesis, we infected A549 cells (a human-derived lung epithelial cell line) in vitro with an adenovirus type 5 (Ad5)-based vector expressing a nuclear targeted beta-galactosidase enzyme (Av1LacZ4). We found that cellular transduction was efficient, resulting in gene delivery to 85.5% +/- 3.9% of the cell monolayer after 96 hr. Importantly, IL-8 mRNA transcript levels in Av1LacZ4-transduced cells were significantly higher than uninfected controls by 24 hr and remained elevated for 96 hr. IL-8 protein secretion from Av1LacZ4-transduced cells was increased for the same period. The Av1LacZ4-transduced A549 cells also showed a neutrophil chemoattractant activity higher than control cells, measurable at 24 hr, and persisting for 96 hr. The chemoattractant activity could be neutralized by a specific monoclonal antibody to IL-8. Whereas Av1LacZ4 transduction induced IL-8 gene expression, there was a lack of expression of MCP-1 by A549 cells. These observations demonstrate that the gene delivery to the airway epithelium using the Ad5-based expression vector results in IL-8 gene activation in these cells, which may contribute to the described inflammatory host response.

Effects of increasing nitrogen intake on nitrogen balance and energy expenditure in nutritionally depleted adult patients receiving parenteral nutrition.

The effects of increasing nitrogen intake were studied in 10 nutritionally depleted patients receiving total parenteral nutrition. After 1 to 2 days on 5% dextrose, the patients received, in random order, intravenous diets containing either a low (180 mg/kg . day) or high (364 mg/kg . day) nitrogen content. Equicaloric amounts of glucose and fat emulsion were given. Total energy intake averaged 33.0 kcal/kg . day corresponding to 1.31 X resting energy expenditure or 1.08 X total energy expenditure. Nitrogen and energy balances were measured daily. Concentrations of glucose, glycerol, fatty acids, triglycerides, urea, insulin and glucagon in plasma, and of beta-hydroxybutyrate in whole blood were measured during the last 2 days of each diet period. An increase in plasma urea was the only change in hormone or substrate concentrations identified. Resting energy expenditure increased approximately 10%, going from 5% dextrose to the low and from the low to the high N diet. Nitrogen balances were 0.21 and 0.61 mg N/kg . day on the low and high N diets. Nitrogen retention of 21% of the increment in intake, three times that seen in normal adult subjects, indicates that the malnourished patients in this study responded in a manner similar to growing organisms. Attainment of markedly positive N balance at, or close to, zero energy balance indicates that lean body mass can be restored without excessive energy intakes which may often be undesirable.

Additional information from percutaneous cutting needle biopsy following fine-needle aspiration in the diagnosis of chest lesions.

OBJECTIVE: To determine the contribution of percutaneous cutting needle biopsy (PNB) subsequent to fine-needle aspiration (FNA) in the diagnosis of chest lesions. DESIGN: A retrospective review of 220 patients who underwent CT-guided FNA followed immediately by PNB performed at our center between 1988 and 1995 was undertaken. Thirty-eight patients were excluded because FNA and/or PNB specimens were nondiagnostic, yielding a study group of 182 patients. RESULTS: A diagnosis of malignancy was made in 141 (77.5%) and nonmalignancy in 41 (22.5%) cases. The yield of histospecific diagnosis due to FNA was marginally higher than PNB in malignant lesions (86.5% vs 78%, respectively). In contrast, PNB was superior to FNA for the histospecific diagnosis of benign lesions (87.8% for PNB vs 31.7% for FNA, p<0.00001) and lymphomas (88% for PNB vs 56% for FNA, p<0.05). In 58.8% of the patients with benign lesions and in 37.5% of the patients with lymphoma, PNB performances altered clinical management, either by avoiding further surgery or allowing specific medical treatment. Pneumothorax occurred in 24.7% of the cases but only five patients (2.7%) required hospitalization. CONCLUSION: PNB is extremely effective for making a specific diagnosis in benign lesions compared with FNA. PNB does not increase the yield of histospecific diagnosis for malignant lesions except for the subset of lymphoma, where it seems to provide important additional information in many instances. We recommend that FNA be performed as the initial procedure, followed by PNB in cases of equivocal diagnosis of carcinoma, for lymphoma and for suspected benign lesions.

An algorithm for pulmonary screening of military pilots in Israel.

BACKGROUND: Medical screening is used routinely to qualify and classify candidates for pilot training. The respiratory system assumes even greater importance owing to the increased stress of flying high-performance aircraft in a hostile environment characterized by high altitude, varying acceleration ("G" forces), and the possibility of rapid decompression. Any respiratory dysfunction may threaten the pilot's health, flight safety, and completion of the mission. Only those candidates with the highest psychophysical score are accepted to undergo special aeromedical screening. Physical suitability is an important factor in the selection and classification of candidates for flight training programs, and pulmonary function testing is central within this screening protocol. METHODS: We developed a respiratory algorithm for this unique screening process. The algorithm represents a practical and efficient approach for large-scale screening of healthy candidates for flight training. The algorithm deals with the major pulmonary health problems encountered in a previously screened healthy population aged 17 to 25 years. If by anamnesis, physical examination results, or baseline spirometry findings there is reason to suspect a respiratory problem that could emerge to endanger the pilot's life, a specially designed evaluation is performed according to the algorithm. We explain, step by step, the basis for each suggested test in order to reach a decision (operational specifications). The pulmonary function studies we recommend are reasonably priced and can be easily and reliably performed by regular medical staff technicians. The major justification for performing pulmonary function studies in a healthy population that has already gone through a preliminary medical screening and has been found fit is to identify occult or latent abnormalities. These abnormalities may have no or minimal clinical expression under ordinary circumstances but, under the stress of flight during the ensuing 5 to 10 years, may produce serious limitation in function. RESULTS: Two cases, seen in the Air Force Medical Center, are presented to illustrate how the algorithm is implemented. The algorithm has been in use for more than 5 years, and has been applied to the screening of several thousand candidates. Follow-up of the accepted candidates has not revealed any significant defects in the decision-making process. CONCLUSION: Use of the algorithm is highly cost-effective since it allows for nonspecialist physicians to carry out pulmonary screening and involves the pulmonary specialist only infrequently, ie, when a particularly complicated and/or borderline case is encountered. It is our contention that a similar algorithm would be useful in many other settings where large-scale screening is required.

Assessment of hazardous dust exposure by BAL and induced sputum.

OBJECTIVES: BAL, an important tool in assessing occupational lung diseases, is unsuitable for screening programs, exposure evaluation, or monitoring hazardous dust because it is an invasive technique. The results of induced sputum (IS) analysis were compared with BAL and evaluated as a possible alternative. METHODS: We compared BAL with IS analysis of 5 workers exposed to asbestos and 14 exposed to silica and hard metals. Pulmonary function tests and BAL were performed by conventional methods. IS induction was performed after a 20-min inhalation of 3.5% saline solution with an ultrasonic nebulizer. Giemsa-stained cytopreparations were differentially counted. T-lymphocyte subsets were analyzed by flow-activated cell sorter, and messenger RNA (mRNA) was transcribed by reverse transcriptase-polymerase chain reaction. Mineralogic particles were analyzed by scanning electron microscopy and polarizing light microscopy and quantified by an analyzer. RESULTS: The percentage of neutrophils was significantly lower in BAL fluid than in IS specimens, whereas no differences were found in the percentage of lymphocytes and subsets profile. Asbestos fibers were found in BAL but not in IS samples from workers exposed to asbestos. Polarizing particles were found in both samples. Similar mineral elements were found in qualitative analysis by scanning electron microscopy. Quantitative studies showed similar size distribution with a small shift toward larger particles in sputum; mRNA showed the same cytokine profile. CONCLUSIONS: A comparison of BAL and IS specimens in the evaluation of the study population yielded similar quantitative and qualitative results. Further research is needed to evaluate the hypothesis that IS, being a noninvasive technique, may be useful in monitoring exposed workers.

Eosinophilic lung reaction to aluminium and hard metal.

A nonsmoker drill polisher with interstitial lung disease is presented. The environmental exposure was mainly to aluminum oxide, aluminum silicate, and hard metals. Bronchoalveolar lavage revealed high eosinophilia, and transbronchial biopsy specimen disclosed interstitial pneumonia with giant cell infiltrates and peribronchiolar accumulation of macrophages laden with opaque dust. Mineralogic studies done from the tissue revealed a high concentration of exogenous particles that were identified as hard metals and aluminum silicate. These findings are compatible with hard metal pneumoconiosis.

Percutaneous core needle biopsy in the diagnosis of mediastinal tumors.

OBJECTIVE: to determine the contribution of percutaneous core cutting needle biopsy (PCNB) in the diagnosis of mediastinal tumors. DESIGN: retrospective review of 70 patients with mediastinal lesions who underwent CT-guided PCNB between 1988 and 1996. RESULTS: PCNB provided adequate material in 62/70 cases, giving a total sample rate of 88.6%. Of these 62 patients, 57 were diagnosed correctly by PCNB whereas 5/62 were misdiagnosed as nonspecific inflammation, providing an overall sensitivity of 91.9%. PCNB established a specific histologic diagnosis in 90.3% of the patients, mainly in cases of lymphoma, bronchogenic carcinoma, and thymoma. Pneumothorax was the most commonly encountered complication (11%). Hemoptysis (30-50 ml) occurred in only one (1.6%) of the patients. CONCLUSION: CT guided PCNB is an easy and safe procedure which can provide a precise diagnosis in the majority of mediastinal tumors and can obviate the need for exploratory thoracic surgery in cases which are medically treatable or non-resectable.

Resting energy expenditure in injured, septic, and malnourished adult patients on intravenous diets.

Energy expenditures of 237 adult patients and 37 normal subjects receiving all nutrition intravenously were analysed retrospectively. Patients were classified as nutritionally depleted (67), post-operative (96), injured (43), or septic/depleted (31). Groups were further divided into those receiving either: (1) only 5% dextrose (D5W); (2) hypocaloric regimens including glucose and amino-acids; and (3) eucaloric or hypercaloric total parenteral nutrition (TPN) which also included fat. Resting energy expenditures (REE) of normal subjects on D5W were only 85% of predicted basal values based on either the Aub-Du Bois or Harris-Benedict equations. During D5W infusions, increases for the patient groups, above these values for normal subjects, varied depending on whether they were based on absolute values or ratios to predicted values. They were: (1) 1-11% for depleted; 1-21% for post-operative; 28-30% for injured; and 18-30% for septic/depleted patients. The average increase in REE with TPN was 10%. Variability within the patient groups was high, reducing the utility of these values as a basis for estimating energy requirements of patients needing artificial nutrition. Coefficients of variation averaged 15% across patient groups when the data were expressed in kJ/kg, and were reduced only slightly, to 12%, when data were expressed as ratios to predicted values. Thus, 1 3 of the patients would differ by more than 12% from mean values, and 1 out of 20 by more than 24%. Properly performed measurements of individual energy expenditure are therefore superior to values predicted from equations or average values previously obtained from patient groups and should be used wherever possible, particularly in the very sick.

Induced sputum compared to bronchoalveolar lavage for evaluating patients with sarcoidosis and non-granulomatous interstitial lung disease.

Bronchoalveolar lavage (BAL), an important tool for evaluating interstitial lung diseases (ILDs), has limited utility due to its invasiveness and the difficulty of performing it in clinically contraindicated patients. We compared BAL with the induced sputum (IS) technique to analyse cells and T lymphocytes in patients with sarcoidosis (SA) and non-granulomatous ILD (NG-ILD). Pulmonary function tests and BAL were performed by conventional methods. IS induction was done 20 sec after inhalation of 3.5% saline with an ultrasonic nebulizer. Giemsa-stained cytopreps were differentially counted. T lymphocyte subsets were analysed by flow activated cell sorter (FACS). Patients with NG-ILD had impaired total lung capacity (TLC). Transbronchial biopsy demonstrated lung fibrosis in NG-ILD and non-caseating granuloma in SA. The differential cell count in both groups demonstrated a significantly lower percentage of neutrophils and a significantly higher percentage of macrophages in BAL than in IS. The IS samples of patients with SA were significantly richer in metachromatic cells and eosinophils, but had a lower percentage of lymphocytes, compared to the BAL samples. The profiles of T cell subsets showed the same pattern, in both samples, in both groups. A CD4/CD8 ratio of 2.5 or greater had a sensitivity of 100% and a specificity of 81.2%, with a positive predictive value of 81.2% to distinguish SA from NG-ILD. IS is an effective non-invasive technique to identify CD4+ inflammation which distinguishes sarcoidosis from other NG-ILDs.

Energy measurements and requirements of critically ill patients.

The energy expenditure of the critically ill patient is influenced by many factors, thus making it difficult to predict. Measurement of energy expenditure in mechanically ventilated patients receiving elevated oxygen concentrations requires a good understanding of the measurement technique and its limitations, whether it be the gas exchange or Fick method. More investigation is needed to better understand the determinants of energy expenditure, as well as the total energy requirements of the critically ill patient.

Percutaneous core needle biopsy vs. fine needle aspiration in diagnosing benign lung lesions.

OBJECTIVE: To determine the diagnostic value of percutaneous core needle biopsy (PCNB) in comparison with fine needle aspiration (FNA) in patients with benign pulmonary lesions. STUDY DESIGN: A retrospective review was undertaken of computed tomography-guided PCNBs and FNAs performed between 1988 and 1997. Both FNA and PCNB biopsies were carried out sequentially at the same visit in every patient. RESULTS: A specific benign diagnosis was made in 10/60 cases (16.7%) by FNA and in 49/60 (81.7%) by PCNB. PCNB findings resulted in significant modification of the diagnosis established by FNA. The only significant complication encountered was pneumothorax, at a rate of 11.7%, which is compatible with that reported in the literature for complications induced by FNA alone. CONCLUSION: Radiologically guided PCNB is a safe procedure, can provide sufficient histologic material for a specific diagnosis of peripheral lung disease and can avoid more-invasive surgical procedures in many cases. Our experience demonstrated that the histologic analysis provided by PCNB can greatly increase the diagnostic accuracy in benign pulmonary diseases as compared with the yield of FNA.

Glycemic load effect on fasting and post-prandial serum glucose, insulin, IGF-1 and IGFBP-3 in a randomized, controlled feeding study.

BACKGROUND/OBJECTIVES: The effect of a low glycemic load (GL) diet on insulin-like growth factor-1 (IGF-1) concentration is still unknown but may contribute to lower chronic disease risk. We aimed to assess the impact of GL on concentrations of IGF-1 and IGF-binding protein-3 (IGFBP-3). SUBJECTS/METHODS: We conducted a randomized, controlled crossover feeding trial in 84 overweight obese and normal weight healthy individuals using two 28-day weight-maintaining high- and low-GL diets. Measures were fasting and post-prandial concentrations of insulin, glucose, IGF-1 and IGFBP-3. In all 80 participants completed the study and 20 participants completed post-prandial testing by consuming a test breakfast at the end of each feeding period. We used paired t-tests for diet component and linear mixed models for biomarker analyses. RESULTS: The 28-day low-GL diet led to 4% lower fasting concentrations of IGF-1 (10.6 ng/ml, P=0.04) and a 4% lower ratio of IGF-1/IGFBP-3 (0.24, P=0.01) compared with the high-GL diet. The low-GL test breakfast led to 43% and 27% lower mean post-prandial glucose and insulin responses, respectively; mean incremental areas under the curve for glucose and insulin, respectively, were 64.3±21.8 (mmol/l/240 min; P<0.01) and 2253±539 (µU/ml/240 min; P<0.01) lower following the low- compared with the high-GL test meal. There was no effect of GL on mean homeostasis model assessment for insulin resistance or on mean integrated post-prandial concentrations of glucose-adjusted insulin, IGF-1 or IGFBP-3. We did not observe modification of the dietary effect by adiposity. CONCLUSIONS: Low-GL diets resulted in 43% and 27% lower post-prandial responses of glucose and insulin, respectively, and modestly lower fasting IGF-1 concentrations. Further intervention studies are needed to weigh the impact of dietary GL on risk for chronic disease.

Diagnosis of intrathoracic lesions: are sequential fine-needle aspiration (FNA) and core needle biopsy (CNB) combined better than either investigation alone?

AIM: To assess the diagnostic accuracy of sequential computed tomography (CT)-guided percutaneous fine-needle aspiration (FNA) and core-needle biopsy (CNB) in comparison with FNA and CNB performed separately for diagnosing intrathoracic lesions. SUBJECTS AND METHODS: Five hundred and eighty-two consecutive patients with thoracic lesions who underwent same-session sequential CT-guided FNA and CNB procedures were studied. The final diagnosis, which was achieved by either agreement of percutaneous procedures with clinical follow-up, bronchoscopy or thoracotomy was available for all cases. The diagnostic yield of the combined FNA+CNB procedures was compared with that of each alone. RESULTS: Adequate samples were obtained in 541 (93%) of FNAs and 513 (88%) of CNBs. Of 582 lesions, 419 (72%) were malignant and 163 (28%) were benign. For malignant lesions, the sensitivity, specificity and accuracy of the procedures were: 376/419 (89.7%), 136/163 (83.4%), and 88% for FNA; 317/419 (75.6%), 138/163 (84.7%), and 78% for CNB; 400/419 (95.5%), 154/163 (94.5%), and 95% for FNA+CNB. The sequential procedures showed significantly better sensitivity, specificity and accuracy compared with either FNA or CNB separately (p<0.003). For the 163 benign lesions, 76 (47%) had a specific benign pathological diagnosis. The diagnosis was obtained in 16/76 (21%) by FNA, in 54/76 (71%) by CNB, and in 60/76 (79%) by FNA+CNB. There was no significant difference between the results of the sequential procedures and CNB alone (p>0.05). CONCLUSIONS: Sequential FNA and CNB improve the diagnostic accuracy of percutaneous CT-guided procedures in malignant lesions. There was only mild improvement, which was not statistically significant, for the diagnosis of benign specific lesions by the sequential procedures compared with the yield of CNB alone.

Pulmonary dysfunction in systemic lupus erythematosus and anti-phospholipid syndrome patients.

OBJECTIVE: To assess and compare parameters of pulmonary function in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) patients. METHODS: Consecutive patients (n = 74) who were free of respiratory symptoms were divided into four groups: 1) SLE (n = 23); 2) SLE with anti-phospholipid antibodies (aPL) (n = 18); 3) SLE with APS (n = 20); and 4) primary APS (PAPS) (n = 13). Pulmonary function testing, single breath diffusion capacity of carbon monoxide (DLCO/SB) and echocardiography studies were performed. Induced sputum cytology was analysed. RESULTS: Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly reduced in SLE compared to PAPS patients (p = 0.039; p = 0.017; p = 0.029, respectively). Elevated pulmonary arterial pressure was observed in two patients with SLE and aPL and in two with SLE and APS. Lymphocyte and eosinophil counts in induced sputum showed no significant differences; however, a trend towards lower CD4 counts in SLE vs. PAPS was noted (p = 0.086), while in patients with both SLE and APS, a low CD4/CD8 ratio was seen. Patients with APS were older than patients without APS (47.12+/-14.86 vs. 34.29+/-12.6, p = 0.0001), while SLE patients were younger than PAPS patients (38.19+/-14.68 vs. 48.53+/-13.97, p = 0.023). CONCLUSION: Abnormal pulmonary functions tests were detected frequently in asymptomatic patients with SLE or PAPS. Although SLE patients were younger, pulmonary function was significantly more impaired in SLE as compared to PAPS patients.

Factors associated with self-evaluated severity of illness and quality of life in male Israeli asthmatic soldiers.

OBJECTIVE: To evaluate whether the asthmatic condition and quality of life of male asthmatic Israeli soldiers deteriorate during army service. METHOD: We retrospectively assessed 178 asthmatic soldiers during service using an adapted version of the Mini Asthma Quality of Life Questionnaire, and compared it to their condition before service. The participants responded additionally to questionnaires assessing psychosocial resources and adjustment to illness. RESULTS: The self-evaluated degree of asthma disease severity (SEDOAD) of the participants deteriorated in the army compared to before service. Soldiers with mild SEDOAD during service, compared to soldiers with severe (and in most cases also moderate) SEDOAD, had less severe medically evaluated and self-evaluated asthma before service. Mild SEDOAD participants showed, additionally, lower inclination towards active seeking of asthma-related information, more favorable health care-related attitudes, less unfavorable effects of their illness on military and extra-military functioning, greater reported pre-enlistment optimism, and a greater belief in their ability to cope successfully with their asthma during service. CONCLUSION: SEDOAD and the quality of life during service are associated not only with pre-enlistment asthma severity, but also with the manner in which the soldier perceives the influence of the illness on his health condition, and the manner in which he copes with this influence.

Induced sputum for diagnosing Pneumocystis carinii pneumonia in HIV patients: new data, new issues.

The complexity of bronchoalveolar lavage (BAL) has motivated the search for noninvasive methodology to retrieve specimens for detecting the presence of various pulmonary diseases. Induced sputum (IS) has been shown to be a reliable tool in terms of sensitivity and specificity comparable to BAL. Investigators from institutions worldwide have published several reports providing evidence in support of one or the other or a combination of both approaches. Among them are studies demonstrating the sensitivity and specificity of IS in diagnosing Pneumocystis carinii pneumonia (PCP) in patients with acquired immunodeficiency syndrome (AIDS). In 1996, highly active antiretroviral therapy was introduced for routine use and the morbidity from opportunistic infections decreased sharply. An earlier study showed that cost-effectiveness depends on the prevalence of a given condition in the population. More recent studies have confirmed that prophylaxis against PCP can be stopped after increasing the CD4 cell count, thus reducing the attractiveness of IS as a preferred method for monitoring the course of disease. This review presents a brief description of the evolution of the bronchoalveolar lavage versus induced sputum controversy and reconsiders the strengths and weaknesses of the earlier arguments in light of newer data that have emerged with regard to Pneumocystis carinii pneumonia in acquired immunodeficiency syndrome.

The association of perennial rhinitis with Trichophyton infection.

Trichophyton was recently reported to be the cause of respiratory allergy in patients with severe bronchial asthma. We describe eight patients with perennial rhinitis in combination with skin or toe-nail infection, in whom Type I hypersensitivity reaction to Trichophyton was confirmed by skin test, RAST and nasal provocation. When treated with oral fungicidal therapy, there was significant improvement in both their skin and nasal symptoms. Local therapy produced only a mild, transient improvement. We emphasize the need for thorough evaluations in patients with respiratory allergies and negative routine skin tests.

Pleural effusion as a presenting symptom of ovarian hyperstimulation syndrome.

Pharmacological ovarian stimulation is an accepted technique for amplifying the normal process of follicular development and maturation. It has been in use for the past decade, especially in cases of infertility. Pleural effusion associated with ovarian hyperstimulation syndrome (OHSS), a complication of this therapy, may be more prevalent than is commonly accepted. Four young women presented to our department with dyspnoea caused by pleural effusion as a result of ovarian hyperstimulation syndrome (OHSS). The diagnosis of OHSS was based on a history of pharmacological ovarian stimulation, clinical and laboratory evidence of ovarian enlargement and exclusion of other potential causes of pleural effusion in young women, such as infections, malignancy, pulmonary embolism and collagen vascular diseases. The fluid characteristics in all cases were exudative, with low to normal LDH. All of these patients required fluid evacuation for symptomatic relief. Resolution was achieved with supportive measures and rest. Ovarian hyperstimulation syndrome may be common enough to warrant routine consideration in the differential diagnosis of pleural effusion in young women.