Showing papers in "American Journal of Respiratory and Critical Care Medicine in 1995"
6,204 citations
TL;DR: Increased mortality is associated with sulfate and fine particulate air pollution at levels commonly found in U.S. cities, although the increase in risk is not attributable to tobacco smoking, although other unmeasured correlates of pollution cannot be excluded with certainty.
Abstract: Time-series, cross-sectional, and prospective cohort studies have observed associations between mortality and particulate air pollution but have been limited by ecologic design or small number of subjects or study areas. The present study evaluates effects of particulate air pollution on mortality using data from a large cohort drawn from many study areas. We linked ambient air pollution data from 151 U.S. metropolitan areas in 1980 with individual risk factor on 552,138 adults who resided in these areas when enrolled in a prospective study in 1982. Deaths were ascertained through December, 1989. Exposure to sulfate and fine particulate air pollution, which is primarily from fossil fuel combustion, was estimated from national data bases. The relationships of air pollution to all-cause, lung cancer, and cardiopulmonary mortality was examined using multivariate analysis which controlled for smoking, education, and other risk factors. Although small compared with cigarette smoking, an association between mor...
2,792 citations
TL;DR: Findings suggest that airway inflammation is already present in infants with CF who are as young as 4 wks, and airway macrophages appear to be a source of this chemokine, and may play a prominent role in early neutrophil influx into the lung.
Abstract: The mechanisms underlying the initiation of lung disease and early respiratory morbidity in cystic fibrosis (CF) are poorly understood. By identifying infants with CF through a statewide neonatal screening program, we investigated whether airway inflammation was present in these infants, with the goal of furthering our understanding of the early events in this lung disease. Bronchoalveolar lavage fluid (BALF) from 16 infants with CF (mean age, 6 mo) and 11 disease control infants (mean age, 12 mo) was examined for the following inflammatory parameters: (1) neutrophil count; (2) activity of free neutrophil elastase; (3) elastase/alpha 1-antiprotease inhibitor complexes; and (4) the level of interleukin-8 (IL-8). We also quantified the spontaneous level of expression of IL-8 mRNA transcripts by airway macrophages. Each index of airway inflammation was increased in the BALF of infants with CF as compared with control infants. In addition, both the number of neutrophils and IL-8 levels were increased in infan...
1,235 citations
TL;DR: Noninvasive positive pressure ventilation administered by nasal or oronasal mask avoids the need for endotracheal intubation, rapidly improves vital signs, gas exchange, and sense of dyspnea, and may reduce mortality in selected patients with acute respiratory failure.
Abstract: Recent studies suggest that noninvasive positive pressure ventilation (NPPV) administered by nasal or oronasal mask avoids the need for endotracheal intubation, rapidly improves vital signs, gas exchange, and sense of dyspnea, and may reduce mortality in selected patients with acute respiratory failure, but few controlled trials have been done. The present study used a randomized prospective design to evaluate the possible benefits of NPPV plus standard therapy versus standard therapy alone in patients with acute respiratory failure. Patients to receive NPPV were comfortably fitted with a standard nasal mask connected to a BiPAP ventilatory assist device (Respironics, Inc., Murrysville, PA) in the patient flow-triggered/time-triggered (S/T) mode, and standard therapy consisted of all other treatments deemed necessary by the primary physician, including endotracheal intubation. The need for intubation was reduced from 73% in the standard therapy group (11 of 15 patients) to 31% in the NPPV group (5 of 16 p...
865 citations
TL;DR: Primary factors associated with increased risk for ARDS in clinical risk subgroups include an elevated Acute Physiologic and Chronic Health Evaluation II (APACHE II) score in patients with sepsis and increased APACHEII and Injury Severity Scores (ISS) in trauma victims.
Abstract: To further understanding of the epidemiology of acute respiratory distress syndrome (ARDS), we prospectively identified 695 patients admitted to our intensive care units from 1983 through 1985 meeting criteria for seven clinical risks, and followed them for development of ARDS and eventual outcome. ARDS occurred in 179 of the 695 patients (26%). The highest incidence of ARDS occurred in patients with sepsis syndrome (75 of 176; 43%) and those with multiple emergency transfusions (> or = 15 units in 24 h) (46 of 115; 40%). Of patients with multiple trauma, 69 of 271 (25%) developed ARDS. If any two clinical risks for trauma were present, the incidence of ARDS was 23 of 57, or 40%. During the study period, we identified 48 patients with ARDS who did not have one of the defined clinical risks, yielding a sensitivity of 79% (179 of 227). Secondary factors associated with increased risk for ARDS in clinical risk subgroups include an elevated Acute Physiologic and Chronic Health Evaluation II (APACHE II) score in patients with sepsis and increased APACHE II and Injury Severity Scores (ISS) in trauma victims. Mortality was threefold higher when ARDS was present (62%) than among patients with clinical risks who did not develop ARDS (19%; p < 0.05). The difference in mortality if ARDS developed was particularly striking in patients with trauma (56% versus 13%), but less in those with sepsis (69% versus 49%). The mortality data should be interpreted with caution, since the fatality rate in ARDS patients appears to have decreased in our institution from the time that these data were collected.(ABSTRACT TRUNCATED AT 250 WORDS)
859 citations
TL;DR: High-resolution computed tomography scans were obtained in 63 subjects referred for surgical resection of a cancer or for transplantation to find out whether the relative area of lung occupied by attenuation values lower than a threshold would be a measurement of macroscopic emphysema.
Abstract: The purpose of this prospective study was to verify whether the percentage area of lung occupied by lowest attenuation values on high-resolution computed tomography (HRCT) scans reflects microscopic emphysema and to compare this quantification with the information yielded by the most widely used pulmonary function tests (PFT). Preoperative HRCT scans were obtained with 1-cm intervals in 38 subjects. With a semiautomatic evaluation procedure, the percentage areas occupied by attenuation values inferior to thresholds ranging from -900 Hounsfield units (HU) to -970 HU were calculated for the lobe or lung to be resected. Emphysema was microscopically quantified by using a computer-based method, measuring the perimeters and interwall distances of alveoli and alveolar ducts. The strongest correlation was found for -950 HU. As a second step, we evaluated possible correlations between PFT and microscopic measurements. Finally, considering the microscopic measurements as a standard, we tried to investigate their relationships with each of the PFT and with the relative area occupied by attenuation values lower than -950 HU for both lungs. This revealed that the diffusing capacity for carbon monoxide associated with HRCT quantification is sufficient to predict microscopic measurements. We concluded that the percentage area of lung occupied by attenuation values lower than -950 HU is a valid index of pulmonary emphysema.
850 citations
Journal Article•
772 citations
TL;DR: Increased serum levels of IL-1 beta and IL-6 in severe PPH are demonstrated, and a role for proinflammatory cytokines in PPH is suggested, and it is suggested that COPD-PH patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease should be considered for lung transplantation.
Abstract: Primary pulmonary hypertension (PPH) is characterized by the proliferation of smooth-muscle cells, fibroblasts, and endothelial cells in the walls of small pulmonary arteries. In order to evaluate a role for proinflammatory cytokines in this process, we studied the concentration of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the serum of 29 patients with severe PPH referred to our center for lung transplantation. Results were compared with those obtained in 15 normal controls and nine patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD-PH). TNF alpha serum levels were within the normal range in each group. This contrasted with increased IL-1 beta serum levels in severe PPH (118 +/- 36 pg/ml, mean +/- SEM) as compared with controls (3 +/- 1 pg/ml, p < 0.001) or COPD-PH patients (3 +/- 1 pg/ml, p < 0.001). IL-6 serum concentrations were also higher in severe PPH (66 +/- 20 pg/ml) than in controls (14 +/- 6 pg/ml, p < 0.01). This study demonstrates increased serum levels of IL-1 beta and IL-6 in severe PPH, and suggests a role for proinflammatory cytokines in PPH.
771 citations
TL;DR: The major findings of this investigation in the 68 subjects were that minimum airway area was significantly smaller in apneic compared with normal subjects and occurred in the retropalatal region, and thickness of the lateral pharyngeal muscular walls rather than enlargement of the parapharyngeAL fat pads was the predominant anatomic factor causing airway narrowing in Apneic subjects.
Abstract: The geometry and caliber of the upper airway in apneic patients differs from those in normal subjects. The apneic airway is smaller and is narrowed laterally. Examination of the soft tissue structures surrounding the upper airway can lead to an understanding of these apneic airway dimensional changes. Magnetic resonance imaging was utilized to study the upper airway and surrounding soft tissue structures in 21 normal subjects, 21 snorer/mild apneic subjects, and 26 patients with obstructive sleep apnea. The major findings of this investigation in the 68 subjects were as follows: (1) minimum airway area was significantly smaller in apneic compared with normal subjects and occurred in the retropalatal region; (2) airway narrowing in apneic patients was predominantly in the lateral dimension; there was no significant difference in the anterior-posterior (AP) airway dimension between subject groups; and (3) distance between the rami of the mandible was equal between subject groups, and thus the narrowing of the lateral dimension was not explained by differences in bony structure; (4) lateral airway narrowing was explained predominantly by larger pharyngeal walls in apneic patients (the parapharyngeal fat pads were not closer together as one would expect if the airway walls were compressed by fat); and (5) fat pad size at the level of the minimum airway was not greater in apneic than normal subjects. At the minimum airway area, thickness of the lateral pharyngeal muscular walls rather than enlargement of the parapharyngeal fat pads was the predominant anatomic factor causing airway narrowing in apneic subjects.
739 citations
TL;DR: Enhanced macrophage production of proinflammatory cytokines and decreased production of the regulatory molecule IL-10 may have important roles in the pathogenesis of CF lung disease.
Abstract: Chronic pulmonary infection with Pseudomonas aeruginosa continues to be the major cause of morbidity and mortality in cystic fibrosis (CF). Several characteristics of CF, including the excessive influx of neutrophils into the airways, cachexia, and hyperglobulinemia, could reflect the effects of cytokines, such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor (TNF-alpha). We hypothesized that these pro-inflammatory cytokines, produced by alveolar macrophages in response to pseudomonas and/or other microorganisms, promote the destructive inflammatory process in the lung. We evaluated bronchoalveolar lavage (BAL) fluid and BAL macrophages from 22 CF patients and 13 healthy control (HC) subjects, measuring soluble TNF-alpha, IL-1 beta, IL-6, and IL-8 and the regulatory molecules TNF soluble receptor (TNF-sR), IL-1 receptor antagonist (IL-1Ra), and IL-10 (cytokine synthesis inhibitory factor). Levels of the proinflammatory cytokines were higher in CF versus HC BAL (p < or = 0.05 for IL-1, TNF, and IL-8; p = 0.06 for IL-6). In contrast, HC BAL contained significantly more IL-10 than CF BAL (p < 0.05), but TNF-sR and IL-1Ra were similar. Immunocytochemistry demonstrated a higher percentage of CF than control BAL macrophages expressing intracellular cytokines (p < 0.05). Thus, enhanced macrophage production of proinflammatory cytokines and decreased production of the regulatory molecule IL-10 may have important roles in the pathogenesis of CF lung disease.
696 citations
Journal Article•
TL;DR: It is concluded that the NA ventilatory strategy can markedly improve the lung function in patients with ARDS, increasing the chances of early weaning and lung recovery during mechanical ventilation.
Abstract: Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals submitted to artificial ventilation. To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome (ARDS) submitted to conventional mechanical ventilation (MV), we evaluated the impact of a new ventilatory strategy directed at minimizing "cyclic parenchymal stretch." After receiving pre-established levels of hemodynamic, infectious, and general care, 28 patients with early ARDS were randomly assigned to receive either MV based on a new approach (NA, consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve, VT < 6 ml/kg, peak pressures < 40 cm H2O, permissive hypercapnia, and stepwise utilization of pressure-limited modes) or a conventional approach (C = conventional volume-cycled ventilation, VT = 12 ml/kg, minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels). Fifteen pa...
TL;DR: The lower airways of asymptomatic chronic obstructive pulmonary disease (COPD) patients can be colonized by bacteria, mainly Haemophilus influenza, Streptococcus pneumoniae, and Moraxella catarrhalis, but the role of lower airway bacteria in stable and exacerbated COPD has not been well defined.
Abstract: The lower airways of asymptomatic chronic obstructive pulmonary disease (COPD) patients can be colonized by bacteria, mainly Haemophilus influenza, Streptococcus pneumoniae, and Moraxella catarrhalis. However, the role of lower airway bacteria in stable and exacerbated COPD has not been well defined. To determine the importance of lower airway bacterial infection in COPD we studied 40 outpatients with stable COPD (Group A: age 61.1 +/- 9.9 yr; [mean +/- SD]; FEV1/FVC 51.7 +/- 12.5) and 29 outpatients with exacerbated COPD (Group B: age 63.4, SD 9.0 yr; FEV1/FVC 52.0, SD 9.6), using the protected specimen brush (PSB) for microbiology sampling. Group A consisted of outpatients with stable COPD having normal or near-normal chest X-rays, with clinical indications for performing fiber-bronchoscopy (pulmonary nodule, remote hemoptysis); Group B consisted of patients with exacerbated COPD who voluntarily accepted lower airway microbiology sampling. To avoid contamination by upper airway flora the PSB was used for bacterial sampling in all the cases and concentrations > or = 1,000 colony-forming units/milliliter (CFU/ml) were considered positive. Results were as follows: Group A: Lung function data in outpatients with stable COPD were lower than the reference values for this population (FVC 2.97 +/- 1.02 L, FVC% 71.4 +/- 22.4, FEV1 1.59 +/- 0.79 L, FEV1% 51.2 +/- 23.0). Positive PSB cultures were obtained in 10 of 40 cases (25%), mainly of H. influenzae and S. pneumoniae. Two of 40 cases had positive cultures at concentrations > or = 10,000 CFU/ml (5.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Although active tuberculosis may be an independent marker of advanced immunosuppression in HIV-infected patients, it may also act as a cofactor to accelerate the clinical course of HIV infection.
Abstract: To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to compare the survival and incidence rate of opportunistic infections in 106 HIV-infected patients with active tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were similar with regard to age, sex, race, previous opportunistic infection, and use of antiretroviral therapy, but they were more likely than control subjects to have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were similar for cases and control subjects (154 versus 153 cells/microliters, respectively). The incidence rate of new AIDS-defining opportunistic infections in cases was 4.0 infections per 100 person-months compared with 2.8 in...
TL;DR: The results emphasize the need for an integrative approach in the assessment and therapeutic management of exercise intolerance, which considers the contribution of muscle weakness to excessive symptoms and reduced work capacity, in addition to the contributions of ventilatory, gas exchange, and circulatory impairments.
Abstract: The contribution of muscle strength to symptom intensity and work capacity was examined in normal individuals and patients with cardiorespiratory disorders. Respiratory muscle strengths (maximal inspiratory and expiratory pressures) and peripheral muscle strengths (leg extension, leg flexion, seated bench press, and seated row) were measured in 4,617 subjects referred for clinical exercise testing. Subjects then rated the intensity of leg effort, discomfort with breathing (dyspnea), and chest pain (Borg scale) during an incremental exercise task (100 kpm/min each minute) to capacity on a cycle ergometer. Subjects were classified into groups on the basis of pulmonary function, drug therapy for cardiac disorders, and the presence of chest pain during exercise with electrocardiographic changes indicative of myocardial ischemia. Respiratory and peripheral muscle strengths, normalized for differences in age, sex, and height, were significantly reduced in patients with cardiorespiratory disorders compared with normal individuals. Muscle strength was a significant contributor to symptom intensity and work capacity in both health and disease; a two-fold increase in muscle strength was associated with a 25 to 30% decrease in the intensity of both leg effort and dyspnea and a 1.4- to 1.6-fold increase in work capacity. These results emphasize the need for an integrative approach in the assessment and therapeutic management of exercise intolerance, which considers the contribution of muscle weakness to excessive symptoms and reduced work capacity, in addition to the contribution of ventilatory, gas exchange, and circulatory impairments.
TL;DR: The distribution of tidal volume (VT) and recruitment was investigated by chest computed tomography (CT) in eight sedated-paralyzed patients with the adult respiratory distress syndrome (ARDS) and found that with increasing PEEP, the VTct distribution decreased significantly in the upper levels, did not change in the middle levels, and increased significantly (p < 0.01) in the lower levels.
Abstract: The distribution of tidal volume (VT) and recruitment was investigated by chest computed tomography (CT) in eight sedated-paralyzed patients with the adult respiratory distress syndrome (ARDS). A CT section was obtained in the supine position at 0, 5, 10, 15, and 20 cm H2O positive end-expiratory pressure (PEEP) and at the corresponding inspiratory plateau pressure (21 +/- 1.8, 26 +/- 1.4, 31 +/- 1.8, 38 +/- 2.1, and 46 +/- 3.2 cm H2O [mean +/- SE]), keeping VT constant. Each CT section was divided along its ventral-dorsal height into 10 equally spaced intervals (levels). Vi(insp) and Vi(exp) were defined as the gas volume for level i (i = 1 to 10) at end-inspiration and at end-expiration, respectively. The following variables were computed at each lung level: (1) distribution of CT section tidal volume (VTct), i.e., the fraction of VT that inflates a given lung level; (2) the plateau-induced and PEEP-induced recruitment, i.e., the amount of lung tissue previously collapsed that inflates at plateau pressu...
TL;DR: In middle-aged men, both snoring and sleep apnea are extremely common, and in this age range both are associated with obesity but not with age, however, a high percentage of snoring is not essential for the occurrence of sleep Apnea, nor does it necessarily indicate that apnea is present.
Abstract: Snoring and sleeping apnea are reportedly associated with morbidity. We used home monitoring (MESAM IV) to measure snoring and sleep apnea in 294 men aged 40 to 65 yr from the volunteer register of the Busselton (Australia) Health Survey. In this group, 81% snored for more than 10% of the night and 22% for more than half the night; 26% had a respiratory disturbance index (RDI) > or = 5, and 10% had an RDI > or = 10. There was a relatively low correlation between percentage of night spent snoring and RDI (rho = 0.47, p or = 5 occurred in a minimum of 3%. Obesity was related to snoring, RDI, and minimum SaO2 (all p < 0.0001). There was no relationship between age and either RDI or snoring, but increased age was related to minimum SaO2 < 85% (p < 0.05). Alcohol consumption was not related to sleep-disordered breathing. Smokers snored for a greater percentage of the night than nonsmokers (41 versus 31%, p = 0.01). We conclude that, in middle-aged men, both sn...
TL;DR: If selection of patients using the new criteria for acute lung injury results in a significant change in the clinical characteristics, risk factors, or predictors of mortality when compared with prior studies of patients with adult respiratory distress syndrome, and to determine if a quantitative index of the severity of lung injury has prognostic value in identifying nonsurvivors of acute Lung injury.
Abstract: A recent North-American-European Consensus Conference proposed new, uniform criteria for the definition of acute lung injury, in part to facilitate earlier identification of patients for clinical trials. However, these criteria have not been evaluated prospectively. We designed a prospective cohort study of 123 consecutive patients with acute lung injury prospectively identified on admission to the adult intensive care units of a tertiary care university hospital. The objectives were to determine if selection of patients using the new criteria for acute lung injury results in a significant change in the clinical characteristics, risk factors, or predictors of mortality when compared with prior studies of patients with adult respiratory distress syndrome (ARDS); and to determine if a quantitative index of the severity of acute lung injury has prognostic value in identifying nonsurvivors of acute lung injury. We used three methods: (1) prospective identification of patients with acute lung injury using a PaO2/FIO2 ratio < 300 and bilateral infiltrates on chest radiograph in the absence of left heart failure; (2) evaluation of the severity of lung injury using a four-point scoring system; and (3) stepwise logistic regression analysis to identify variables significantly associated with hospital mortality. Overall hospital mortality was 58%. Sepsis was the most common clinical disorder (50/123 or 41%) associated with the development of acute lung injury. Using the new definition for acute lung injury, 66 of the 123 patients were enrolled with a PaO2/FIO2 ratio between 150 and 299; 57 of the 123 patients had a PaO2/FIO2 < 150 at the time of entry into the study.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: It is concluded that VCD can masquerade as asthma and that it often coexists with asthma.
Abstract: Vocal cord dysfunction (VCD) is a respiratory condition characterized by adduction of the vocal cords with resultant airflow limitation at the level of the larynx. Previously, this condition was described in case reports and in small series. This study reviews all patients hospitalized from 1984 through 1991 in whom VCD was diagnosed. Demographic, historical, physiologic, laboratory, and psychiatric factors were statistically analyzed. Ninety-five patients met the criteria for proved VCD; of these, 53 also had asthma. All patients had laryngoscopic evidence of paradoxical vocal cord motion, with inspiratory and/or early expiratory vocal cord adduction. The patients with VCD without asthma were predominantly young women. In these patients, asthma had been misdiagnosed for an average of 4.8 years. Their medications were identical to those of a control group of patients with severe asthma. Thirty-four of the 42 patients with VCD without asthma were receiving prednisone regularly at an average daily dose of 29.2 mg. Medical utilization was enormous with the VCD group, averaging 9.7 emergency room visits and 5.9 admissions in the year prior to presentation. Also, 28% of the patients with VCD had been intubated. We conclude that VCD can masquerade as asthma and that it often coexists with asthma. This study helps to define the historical and clinical features of VCD.
TL;DR: It is demonstrated that nitrogen-derived oxidants are formed in human acute lung injury and suggested that peroxynitrite may be an important oxidant in inflammatory lung disease.
Abstract: Oxidant-mediated toxicity resulting from acute pulmonary inflammation has been demonstrated in acute lung injury. A potent biological oxidant, peroxynitrite, is formed by the near diffusion-limited reaction of nitric oxide with superoxide. In addition to having hydroxyl radical-like oxidative reactivity, peroxynitrite is capable of nitrating phenolic rings, including protein-associated tyrosine residues. Nitric oxide does not directly nitrate tyrosine residues, therefore, demonstration of tissue nitrotyrosine residues infers the action of peroxynitrite or related nitrogen-centered oxidants. Lung tissue was obtained from formalin-fixed, paraffin-embedded autopsy specimens, and specific polyclonal and monoclonal antibodies to nitrotyrosine were visualized by diaminobenzidene-peroxidase staining. Acute lung injury resulted in intense staining throughout the lung, including lung interstitium, alveolar epithelium, proteinaceous alveolar exudate, and inflammatory cells. In addition, staining of the vascular endothelium and subendothelial tissues was present in those patients with sepsis-induced acute lung injury. Antibody binding was blocked by coincubation with nitrotyrosine or nitrated bovine serum albumin but not by aminotyrosine, phosphotyrosine, or bovine serum albumin. Reduction of tissue nitrotyrosine to aminotyrosine by sodium hydrosulfite also blocked antibody binding. In control specimens with no overt pulmonary disease, there was only slight staining of the alveolar septum. These results demonstrate that nitrogen-derived oxidants are formed in human acute lung injury and suggest that peroxynitrite may be an important oxidant in inflammatory lung disease.
TL;DR: It is concluded that re-intubation is a risk factor for ventilator-associated pneumonia and might be avoided in a substantial number of cases and semirecumbency during the period between extubation and re-intsubation may play a role in nosocomial pneumonia development in patients who need re- Intubation.
Abstract: In order to confirm that re-intubation can be a risk factor of nosocomial pneumonia in mechanically ventilated patients, a case-control study was performed. Forty consecutive patients needing re-intubation were selected as cases. Each case was paired with a matched control for the previous duration of mechanical ventilation (+/- 2 d). Nineteen (47%) of the cases developed pneumonia after re-intubation compared with 4 (10%) of the controls (odds ratio [OR] = 8.5; 95% confidence interval [CI] 1.7 to 105.9; p = 0.0007). After adjusting for age, sex, and presence of prior bronchoscopy, the conditional logistic regression analysis demonstrated that re-intubation was the only significant factor related to the development of pneumonia (OR: 5.94; 95% CI 1.27 to 22.71; p = 0.023). Sixteen (73%) of the 22 patients lying semirecumbent during the interval between extubation and re-intubation developed nosocomial pneumonia versus three (16%) of the 18 in supine position (p = 0.001). These results indicate that semirec...
TL;DR: The data suggest that as long as the inflammatory reaction is predominantly of neutrophils there is no destruction of the lung, and the extent of lung destruction becomes evident, and its extent is directly related to the number of alveolar macrophages and T-lymphocytes/mm3.
Abstract: The prevalent theory in the pathogenesis of emphysema proposes that increased numbers of activated neutrophils and/or alveolar macrophages produce large amounts of proteases, an activity that cannot be regulated by alpha 1-antiproteases, resulting in lung destruction. However, the cells in the lung parenchyma of smokers have not been properly identified. We characterized and quantitated the inflammatory cell load in the lungs of smokers and correlated these findings with the degree of lung destruction. Twenty-one patients, six nonsmokers and 15 smokers, undergoing lung resection were studied. Lungs or lobes were fixed and stained for light microscopy and neutrophil identification and immunohistochemically stained for identification of lymphocytes and macrophages. By point counting, we determined the extent of emphysema by the volume density of the lung parenchyma (Vvalv), and the different cell numbers per cubic millimeter in all lungs. In nonsmokers Vvalv was greater than in smokers. The number of neutrophils/mm3 of lung correlated directly with the Vvalv, (r = 0.71, p < 0.01), whereas the number of alveolar macrophages (r = -0.70) and T-lymphocytes (r = -0.78) correlated negatively with the Vvalv. The number of T-lymphocytes correlated negatively with the number of neutrophils (r = -0.58) and positively with the numbers of alveolar macrophages (r = 0.77). Our data suggest that as long as the inflammatory reaction is predominantly of neutrophils there is no destruction of the lung. However, the extent of lung destruction becomes evident, and its extent is directly related to the number of alveolar macrophages and T-lymphocytes/mm3. We conclude that the T-lymphocyte might be importantly implicated in the pathogenesis of emphysema in smokers.
TL;DR: In patients with CHF, CSR-CSA is associated with elevated sympathoneural activity, which can be reduced by NCPAP, which was attenuated in the NCP AP but not in the control group.
Abstract: We hypothesized that (1) patients with congestive heart failure (CHF) and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) would have greater nocturnal urinary and daytime plasma norepinephrine concentrations (UNE and PNE, respectively) than those without CSR-CSA because of apneas, hypoxia and arousals from sleep and (2) attenuation of CSR-CSA by nasal continuous positive airway pressure (NCPAP) would reduce UNE and PNE concentrations. Eighteen patients with and 17 without CSR-CSA (Non-CSR-CSA group) were studied. Left ventricular ejection fraction was similar in the two groups, but overnight UNE and awake PNE concentrations were greater in the CSR-CSA group (30.2 +/- 2.5 nmol/mmol creatinine and 3.32 +/- 0.29 nmol/L) than in the Non-CSR-CSA group (15.8 +/- 2.1 nmol/mmol creatinine, p < 0.005, and 2.06 +/- 0.56 nmol/L, p < 0.05, respectively). Patients with CSR-CSA were randomized to a control group or to nightly NCPAP for 1 mo. CSR-CSA was attenuated in the NCPAP but not in the control group. The NCPAP group experienced greater reductions in UNE and PNE concentrations (-12.5 +/- 3.3 nmol/mmol creatinine and -0.74 +/- 0.40 nmol/L) than did the control group (-1.3 +/- 2.8 nmol/mmol creatinine, p < 0.025 and 1.16 +/- 0.66 nmol/L, p < 0.025, respectively). In conclusion, in patients with CHF, CSR-CSA is associated with elevated sympathoneural activity, which can be reduced by NCPAP.
TL;DR: Cigarette smoking decreased exhaled NO, suggesting that it may inhibit the enzyme NO synthase, and this effect may contribute to the increased risks of chronic respiratory and cardiovascular disease in cigarette smokers.
Abstract: Cigarette smoking is associated with an increased risk of respiratory tract infections, chronic airway disease, and cardiovascular diseases, all of which may be modulated by endogenous nitric oxide (NO). We have investigated whether cigarette smoking reduces the production of endogenous NO. We compared exhalations of 41 current cigarette smokers with normal lung function and 73 age-matched non-smoking controls. Peak exhaled NO levels were measured by a modified chemiluminescence analyzer. The effects of inhaling a single cigarette in smokers were also measured. In control subjects we also measured the effects of inhalation of NO itself and carbon monoxide, both constituents of tobacco smoke. Peak exhaled NO concentrations were significantly reduced in smokers (42 +/- 3.9 compared with 88 +/- 2.7 parts per billion in nonsmokers, p < 0.01), with a significant relation between the exhaled NO and cigarette consumption (r = 0.77, p < 0.001). Smoking a single cigarette also significantly (p < 0.02), but transiently, reduced exhaled NO. Inhalation of carbon monoxide and NO had no effect on exhaled NO in normal subjects. Cigarette smoking decreased exhaled NO, suggesting that it may inhibit the enzyme NO synthase. Since endogenous NO is important in defending the respiratory tract against infection, in counteracting bronchoconstriction and vasoconstriction, and in inhibiting platelet aggregation, this effect may contribute to the increased risks of chronic respiratory and cardiovascular disease in cigarette smokers.
TL;DR: Nasal positive-pressure ventilation may be a useful addition to LTOT in stable hypercapnic COPD as compared with run-in and oxygen alone, and quality of life with oxygen plus NPSV was significantly better than with oxygen alone.
Abstract: Non-invasive ventilation has been used in chronic respiratory failure due to chronic obstructive pulmonary disease (COPD), but the effect of the addition of nasal positive-pressure ventilation to long-term oxygen therapy (LTOT) has not been determined. We report a randomized crossover study of the effect of the combination of nasal pressure support ventilation (NPSV) and domiciliary LTOT as compared with LTOT alone in stable hypercapnic COPD. Fourteen patients were studied, with values (mean +/- SD) of Pao2 of 45.3 +/- 5.7 mm Hg, PaCO2 of 55.8 +/- 3.6 mm Hg, and FEV1 of 0.86 +/- 0.32 L. A 4 wk run-in period (on usual therapy) was followed by consecutive 3-mo periods of: (1) oxygen therapy alone, and (2) oxygen plus NPSV in randomized order. Assessments were made during run-in and at the end of each study period. There were significant improvements in daytime arterial PaO2 and PaCO2, total sleep time, sleep efficiency, and overnight PaCO2 following 3 mo of oxygen plus NPSV as compared with run-in and oxygen alone. Quality of life with oxygen plus NPSV was significantly better than with oxygen alone. The degree of improvement in daytime PaCO2 was correlated with the improvement in mean overnight PaCO2. Nasal positive-pressure ventilation may be a useful addition to LTOT in stable hypercapnic COPD.
TL;DR: Nutritional supplementation in combination with a short course of anabolic steroids may enhance the gain in FFM and respiratory muscle function in depleted patients with COPD without causing adverse side effects.
Abstract: Nutritional depletion commonly occurs in patients with COPD, causing muscle wasting and impaired physiologic function. Two hundred seventeen patients with COPD participated in a placebo-controlled, randomized trial investigating the physiologic effects of nutritional intervention alone (N) for 8 wk or combined with the anabolic steroid nandrolone decanoate (N + A). Nandrolone decanoate or placebo (P) was injected intramuscularly (women, 25 mg; men, 50 mg) in a double-blind fashion on Days 1, 15, 29, and 43. Nutritional intervention consisted of a daily high caloric supplement (420 kcal; 200 ml). Also, all patients participated in an exercise program. In the depleted patients, both treatment regimens induced a similar significant body weight gain (2.6 kg) but different body compositional changes. Particularly in the last 4 wk of treatment, weight gain in the N group was predominantly due to an expansion of fat mass (p < 0.03 versus P and N + A), whereas the relative changes in fat-free mass (FFM) and other measures of muscle mass were more favorable in the N + A group (p < 0.03 versus P). Maximal inspiratory mouth pressure improved within both treatment groups in the first 4 wk of treatment, but after 8 wk only N + A was significantly different from P (p < 0.03). Nutritional supplementation in combination with a short course of anabolic steroids may enhance the gain in FFM and respiratory muscle function in depleted patients with COPD without causing adverse side effects.
TL;DR: The association of chronic obstructive pulmonary disease (COPD) and sleep apnea syndrome (SAS) is likely to occur in a number of patients, and a large series of patients selected solely on the basis of a confirmed diagnosis of SAS are prospectively investigated.
Abstract: The association of chronic obstructive pulmonary disease (COPD) and sleep apnea syndrome (SAS), which are both frequent diseases, is likely to occur in a number of patients. We have prospectively investigated a large series (n = 265) of patients who were selected solely on the basis of a confirmed diagnosis of SAS (apnea + hypopnea index > 20/hr). An obstructive spirographic pattern, defined by an FEV1/VC ratio or = 45 mm Hg) was observed in 8 of 30 overlap patients and in 19 of 235 of the remainder. The pulmonary artery mean pressure (PAP) was higher in overlap patients both at rest (20 +/- 6 versus 15 +/- 5 mm Hg, p < 0.01) and during steady-state exercise (37 +/- 12 versus 29 +/- 10 mm Hg, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Rhinoviral colds are associated with a bronchial mucosal lymphocytic and eosinophilic infiltrate that may be related to changes in airway responsiveness and asthma exacerbations.
Abstract: Human rhinoviruses (HRV) cause the majority of common colds and are etiologically linked with changes in lower airways physiology and asthma exacerbations. We hypothesized that changes in bronchial mucosal inflammatory cell populations may be responsible for HRV-induced changes in airway reactivity. We examined bronchial mucosal biopsies during experimental infections with HRV serotype 16 and measured changes in histamine reactivity. Seventeen adult volunteers (six atopic asthmatics) had baseline measurements of histamine reactivity and fiberoptic bronchoscopic biopsies, followed 2 wk later by viral inoculation. Further bronchial biopsies were taken on Day 4 of the infection and 6 to 10 wk later. Mast cells, eosinophils, lymphocytes, and neutrophils were quantified by immunohistochemical techniques. Infection was documented by viral culture, seroconversion, and symptoms. An increase in histamine responsiveness during the cold (p = 0.048) was accompanied by increases in submucosal lymphocytes (p = 0.050). There was a subsequent decrease in submucosal and epithelial lymphocytes in convalescence (p = 0.028; p = 0.030). There was an increase in epithelial eosinophils with the cold (p = 0.042), and in asthmatics this appeared to persist into convalescence. A peripheral blood lymphopenia correlated with increased responsiveness (r = 0.062, p = 0.014). Rhinoviral colds are associated with a bronchial mucosal lymphocytic and eosinophilic infiltrate that may be related to changes in airway responsiveness and asthma exacerbations.
TL;DR: This was a genetic-epidemiologic study that assessed the distribution of SDB in families identified through a proband with diagnosedSleep apnea and among families in the same community with no relative with known sleep apnea.
Abstract: An inherited basis for sleep-disordered breathing (SDB) has been suggested by reports of families with multiple affected members and by a previous study of the familial aggregation of symptoms of SDB. In this study, we quantify and characterize the aggregation of SDB and assess the degree to which familial similarities may be independent of obesity. This was a genetic-epidemiologic study that assessed the distribution of SDB in families identified through a proband with diagnosed sleep apnea and among families in the same community with no relative with known sleep apnea. SDB was assessed with overnight in-home monitoring of airflow, oxygen saturation, chest wall impedance, heart rate, and body movement. Standardized questionnaires were used to assess symptoms, and weight, height, and neck circumference were measured directly. Intergenerational and intragenerational correlation coefficients and pairwise odds ratios (ORs) were calculated with adjustment for proband sampling. In toto, 561 members of 91 families were studied: (1) 47 subjects with laboratory-confirmed SDB (index probands), (2) 44 community control subjects, and (3) the spouses and relatives of 1 and 2. Of all 91 families, 32 (35%) had two or more members with SDB, 30 (33%) had one affected member, and 29 had no affected members. SDB was more prevalent in the relatives of index probands (21%) than among neighborhood control subjects (12%) (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)