Showing papers in "The American review of respiratory disease in 1990"

Mucosal inflammation in asthma.

Abstract: Over the past decade, it has become increasingly recognized that airways inflammation is one of the major components of asthma. Until recently, measurements of bronchial responsiveness and mediators of allergic reactions were the only methods of studying pathogenetic mechanisms in asthma. With improved diagnostic procedures such as fiberoptic bronchoscopy, it has become possible to investigate these mechanisms and the resulting inflammatory changes in situ. BAL has highlighted the presence of mast cells and eosinophils and has given proof of their mediator participation in airways inflammation and hyperresponsiveness. Endobronchial biopsies have so far yielded results that are similar to those obtained from postmortem studies, although it appears that there are varying degrees of inflammation in living asthmatics. Even in mild disease, the histopathologic features of bronchial asthma are consistent with chronic inflammation. Indirect evidence obtained from allergen challenge leading to increased bronchial hyperresponsiveness during LAR, and direct evidence of inflammatory cells and their mediators in the airway mucosa and lumen after allergen challenge argue for an active role of cells in bringing about inflammatory changes. At present, however, it is not possible to relate precisely the findings obtained by bronchoscopy to the clinical presentation and progression of asthma. Cell activation with production of potent mediators of inflammation may be more relevant to inflammation than the simple presence of these cells in the airways. Almost all the inflammatory cells present in the bronchial wall and lumen have been implicated in the pathogenesis of mucosal inflammation in asthma, but with our current state of knowledge, none can be singled out as the most important contributor. The mast cell was the first to be investigated in depth, and despite the accumulation of large amounts of data concerning its ultrastructure and function, it remains uncertain to what extent this cell is involved in inflammatory responses. Thus, while its main role appears to be that of initiator of allergen-induced responses, the eosinophil has attracted more attention as a proinflammatory cell rather than as an antiinflammatory cell with a capacity to be selectively recruited from the circulation in response to IgE-dependent signals. The eosinophil secretes potent mediators that cause damage to the bronchial epithelium and lead to bronchoconstriction. The role of other cells is at present not as well defined.(ABSTRACT TRUNCATED AT 400 WORDS)

Macrophages and polymorphonuclear neutrophils in lung defense and injury

Abstract: Phagocytes, in particular macrophages and PMN, are now recognized as major components of inflammatory and immunologic reactions in the lung. Normally, macrophages represent the majority of phagocytes in the lower respiratory tract. These lung macrophages are morphologically and functionally heterogenous and include alveolar, interstitial, intravascular, and airway macrophages, each with characteristic morphologic and functional features. Through the presence of surface receptors for numerous ligands and through their large number of secretory products, lung macrophages can respond to environmental factors and account for most of the clearance of microparticles and microorganisms in the distal airways and the alveolar spaces. In addition, macrophages also play an important role in inflammatory processes through the release of oxygen radicals and proteolytic enzymes. Through the release of several cytokines, i.e., growth-promoting and inhibiting factors, lung macrophages may also influence both matrix damage and repair processes. Macrophages can also contribute to the alveolitis by recruitment of inflammatory and immune cells. This latter contribution is best demonstrated in migration movement of PMN. The normal distal airways generally contain a small number of PMN, but the pulmonary vascular bed represents a large reservoir of PMN. Some of them are in intimate contact with the endothelium, forming the so-called marginating pool of PMN. Because the capillary lumen is separated only from the alveolar space by a monolayer of endothelial and epithelial cells on each side of a thin interstitial matrix, it is likely that some inhibitory mechanism exists to prevent PMN from migrating towards the alveolar space. Such inhibitors of PMN migration are present both in serum and in the alveolar space, some being released by alveolar macrophages. However, alveolar macrophages can also secrete factors called chemotaxins that attract PMN to the airways, and this supports a central role for alveolar macrophages in the regulation of PMN traffic in the lungs. Thus, secretory products of alveolar macrophages are part of the regulatory mechanisms of PMN mobility and adherence that appears to be crucial in the initiation of some inflammatory reactions. The contribution of phagocytes to the defense against infection and tumor has been documented mostly in vitro. Thus, both oxygen radicals, in particular hydroxyl radicals and proteases such as lysozyme, are potent bactericidal agents. That phagocytes are also important defenders of the lungs in vivo is best supported by the observations in immunodeficient patients and animal models.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnosis and Treatment of Disease Caused by Nontuberculous Mycobacteria

Abstract: Diagnostic Criteria of Nontuberculous Mycobacterial Lung Disease For patients with a cavitary infiltrate: Two or more sputums or bronchial washings that are acid-fast bacilli smear positive and/or produce moderate to heavy growth on culture.Exclusion of other reasonable causes for the disease.II. For patients with a noncavitary infiltrate: Two or more sputums or bronchial washings that are acid-fast bacilli smear positive and/or produce moderate to heavy growth on culture.The isolate is Mycobacterium avium complex or M. kansasii and cannot be cleared from the sputum with either bronchial hygiene or 2 wk of drug therapy.Exclusion of other reasonable causes for the disease.For patients with a cavitary or noncavitary infiltrate whose sputum evaluations are nondiagnostic or another disease cannot be excluded: 1. Lung biopsy yields a NTM.2. The biopsy shows mycobacterial histopathologic features (i.e., granulomatous inflammation) and two or more sputums are positive for a NTM even in low numbers.

Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients.

Abstract: Seventy-eight (24%) episodes of nosocomial pneumonia (NP) were detected in 322 consecutive mechanically ventilated patients admitted to a 1,000-bed teaching hospital from April 1987 through May 1988 to assess the incidence, risk, and prognosis factors of NP acquired during mechanical ventilation (MV). The risk and prognosis factors for developing NP during MV were studied using both univariate and multivariate statistical techniques. Multivariate analysis selected the following variables significantly associated with a higher risk for developing ventilator-associated pneumonia: more than one intubation during MV (p = 0.000012), a prior episode of aspiration of gastric content (p = 0.00018), a MV period longer than 3 days (p = 0.015), the presence of chronic obstructive pulmonary disease (COPD) (p = 0.048), and the use of positive end-expiratory pressure (PEEP) during MV (p = 0.092). The presence of an ultimately or rapidly fatal underlying disease (p = 0.0018), worsening of acute respiratory failure caused by pneumonia (p = 0.0096), the presence of septic shock (p = 0.016), an inappropriate antibiotic treatment (p = 0.02), and the type of intensive care unit (ICU) hospitalization (noncardiac surgery and nonsurgical ICU compared with post-cardiac surgery ICU) (p = 0.08) were those factors selected by a stepwise logistic regression analysis as independently worsening the prognosis. The overall fatality rate was 23% (73 of 322). The mortality of patients with NP was higher (33%; 26 of 78; p less than 0.01) when compared with fatality rates of patients without NP (19%; 47 of 244).(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma.

Abstract: We have used immunohistochemistry and monoclonal antibodies to analyze the phenotypic composition and activation status of the cellular infiltrate of bronchial biopsies obtained by fiber optic bronchoscopy of 11 atopic asthmatic subjects (FEV1 % predicted range 78 to 114), 9 atopic nonasthmatic control subjects, and 10 normal healthy subjects. Examination of mucosal biopsies obtained from both central (level I) and subsegmental (level II) bronchi showed that the highest number of CD45-, DC3-, DC4-, and CD8-positive cells were found in the group with asthma. There was a significant increase in the number of interleukin-2 receptor (CD25)-positive cells (a marker of lymphocyte activation) at airway level I in the asthmatic group compared with both nonasthmatic atopic (p < 0.05) and normal control subjects (p < 0.01). Eosinophil numbers were significantly increased in asthma at both airway levels and at airway level II in the nonasthmatic atopic group when compared with normal healthy control subjects (p < 0....

Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy.

Abstract: A successful, systematic, anatomic, diagnostic protocol for evaluating patients with chronic cough was presented in 1981 To determine whether it was still valid, we prospectively evaluated, over a 22-month interval, 102 consecutive and unselected immunocompetent patients complaining of cough an average of 53 ± 97 months (range, 3 wk to 50 yr) Utilizing the anatomic, diagnostic protocol modified to include prolonged esophageal pH monitoring (EPM), the causes of cough were determined in 101 of 102 (99%) patients, leading to specific therapy that was successful in 98% Cough was due to one condition in 73%, two in 23%, and three in 3% Postnasal drip syndrome was a cause 41% of the time, asthma 24%, gastroesophageal reflux (GER) 21%, chronic bronchitis 5%, bronchiectasis 4%, and miscellaneous conditions 5% Cough was the sole presenting manifestation of asthma and GER 28 and 43% of the time, respectively While history, physical examination, methacholine inhalational challenge (MIC), and EPM yielded the mo

Intact epithelial barrier function is critical for the resolution of alveolar edema in humans.

Abstract: Within 15 min of endotracheal intubation, the resolution of pulmonary edema was studied over the next 12 h in 34 mechanically ventilated patients by (1) serial measurements of the alveolar-arterial oxygen difference, (2) the extent of edema on the initial and follow-up chest radiograph, and (3) by an initial and final measurement of total protein and albumin concentration in sequential samples of pulmonary edema fluid. Based on the oxygenation and chest radiographic data, 24 patients clinically improved and 10 patients did not improve. In the 10 patients who did not clinically improve (3, hydrostatic edema; 7, permeability edema), there was no change in the final edema fluid protein concentration (4.1 +/- 1.1 g/100 ml) compared with the initial edema fluid protein concentration (4.2 +/- 1.0 g/100 ml) (p = ns). However, in the 24 patients who clinically improved (15, hydrostatic edema; 9, permeability edema), there was an increase in every patient's final edema protein concentration (5.6 +/- 2.3 g/100 ml) compared with their initial edema protein concentration (3.8 +/- 1.2 g/100 ml) (p less than 0.01). In 13 of these 24 patients, the final edema fluid concentration (7.3 +/- 1.6 g/100 ml) exceeded the final plasma protein concentration (5.6 +/- 0.8 g/100 ml) by a mean value of 1.7 g/100 ml protein. The data provide the first evidence in humans to support the hypothesis that active ion transport across the alveolar epithelial barrier is the primary mechanism for clearance of edema fluid from the air spaces of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics.

Abstract: Several short-term studies have shown that inhaled steroids can reduce airway hyperresponsiveness in asthma. To evaluate whether prolonged treatment can bring about full recovery, this double-blind, randomized, controlled trial examined the effect of budesonide, 400 µg daily for 1 yr, on airway hyperresponsiveness. The time course and characteristics of improvements and associated changes in clinical asthma severity were also evaluated. Thirty-two stable adult asthmatics, requiring bronchodilators alone, were selected. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, daily bronchodilator use, and number of asthma exacerbations. Patients receiving budesonide showed a fourfold mean improvement in airway responsiveness compared with those receiving placebo (p < 0.0005), whose responsiveness remained very stable. Fifteen of the 16 budesonide subjects improved and 5 returned to the normal range. Largest improveme...

Genetics of asthma and hay fever in Australian twins.

Abstract: The occurrence of self-reported asthma/wheezing and hay fever among 3,808 pairs of twins from the Australian National Health and Medical Research Council Twin Registry was examined for evidence of genetic transmission by path analytic methods. The cumulative prevalence of asthma or wheezing was 13.2% and of hay fever, 32%. There were significant correlations in liability to reported disease among twins, and these were higher in monozygotic twins (MZ) (r = 0.65) than in dizygotic twins (DZ) (r = 0.25), and in male MZ twins (r = 0.75) compared with female MZ twins (r = 0.60). Analysis under the assumptions of the classic twin model suggested that there were genetic factors common to asthma and hay fever, with a correlation in genetic liability to the traits of 0.52 for men and 0.65 for women. These genes acted substantially in a nonadditive fashion in men but not in women. As the genetic correlation was significantly less than unity, this implied additional genetic factors influencing either or both diseases individually. The estimated heritability of these diseases was 60 to 70% in this population. Environmental causes of both diseases also were correlated (r = 0.53 for men and 0.33 for women). Cigarette smoking was only weakly associated with wheezing.

Continuous positive airway pressure reduces work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease

Abstract: Dynamic hyperinflation and the development of intrinsic positive end-expiratory pressure (PEEPi) are commonly observed in patients with severe chronic obstructive pulmonary disease (COPD) and acute respiratory failure. The presence of intrinsic PEEP acts as an inspiratory threshold load, and contributes significantly to the observed increase in work and oxygen cost of breathing. The present study examined the effects of continuous positive airway pressure (CPAP) (at 5, 10, and 15 cm H2O) and its ability to reduce the mechanical load imposed by PEEPi on breathing pattern, work of breathing, and dyspnea in seven patients with severe COPD during weaning from mechanical ventilation. Tidal volume remained stable at all levels of applied pressure. Breathing frequency was also stable except for a small (12%) decrease during CPAP of 15 cm H2O. Inspiratory pulmonary resistance and elastance were unaltered by the application of CPAP. There were progressive reductions in the inspiratory work of breathing as the leve...

Distinguishable types of dyspnea in patients with shortness of breath

Abstract: Dyspnea frequently accompanies a variety of cardiopulmonary abnormalities. Although dyspnea is often considered a single sensation, alternatively it may encompass multiple sensations that are not well explained by a single physiologic mechanism. To investigate whether breathlessness experienced by patients represents more than one sensation, we studied 53 patients with one of the following seven conditions: pulmonary vascular disease, neuromuscular and chest wall disease, congestive heart failure, pregnancy, interstitial lung disease, asthma, and chronic obstructive pulmonary disease. Patients were asked to choose descriptions of their sensation(s) of breathlessness from a dyspnea questionnaire listing 19 descriptors. Cluster analysis was used to identify natural groupings among the chosen descriptors. We found that patients could distinguish different sensations of breathlessness. In addition, we found an association between certain groups of descriptors and specific conditions producing dyspnea. These findings concur with those in an earlier study in normal volunteers in whom dyspnea was induced by various stimuli. We conclude that different types of dyspnea exist in patients with a variety of cardiopulmonary abnormalities. Furthermore, different mechanisms may mediate these various sensations.

Predictors of Asthma and Persistent Wheeze in a National Sample of Children in the United States. Association With Social Class, Perinatal Events, and Race

Abstract: This study analyzes data from the Second National Health and Nutritional Examination Survey to determine whether black children are more likely to have asthma or wheeze, even after adjusting for environmental and socioeconomic exposures. For children 6 months to 11 yr of age, the unadjusted prevalence for asthma was 3.0% among white children and 7.2% among blacks; prevalence of frequent wheeze was 6.2% among whites and 9.3% among blacks. In a logistic regression model including race, age, and sex, the relative odds (RO) of asthma for black children as compared to white children were 2.5 (95% confidence interval [CI], 1.9 to 3.4). Other predictors of asthma in a stepwise logistic regression included age, sex (boys versus girls, RO = 1.4), younger maternal age (2 standard deviation [SD] drop in age, RO = 1.4), residence in the central city (RO = 1.6), and family income (RO for the lowest versus highest tertile, RO = 1.7). After adjusting for these risk factors, age and sex, black children still had a 1.7 RO...

CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status.

Abstract: Lymphocytes are prominent among the inflammatory cells infiltrating the asthmatic airways, and several studies have suggested that cell-mediated immunity may play a role in the pathogenesis of chronic asthma. We have measured (1) the expression of activation markers on the CD4+ and CD8+ T-lymphocyte phenotypic subsets in the peripheral blood of patients hospitalized with acute severe asthma (“status asthmaticus”), and (2) the serum concentrations of two proteins elaborated by activated T-lymphocytes (interferon-γ and the soluble interleukin-2 receptor). The results were compared with those in control subjects (mild asthma, chronic obstructive airway disease, and normal). CD4+ lymphocytes from patients with acute severe asthma showed significant increases in the expression of three surface proteins associated with lymphocyte activation (interleukin-2 receptor [IL-2R], class II histocompatibility antigen [HLA-DR], and “very late activation” antigen [VLA-1]) as compared with those from normal control subject...

The Influence of Increasing Ventilatory Effort on Arousal from Sleep

Abstract: Arousal from sleep in response to asphyxia can be a lifesaving event. However, the mechanisms responsible for this important arousal response are uncertain. A unifying hypothesis is that arousal results from the increased respiratory effort that occurs as a result of ventilatory stimulation. If this is true, the magnitude of this effort during the breaths immediately preceding arousal from sleep should be similar regardless of the stimulus. Therefore, the negative inspiratory pleural pressure during the breaths preceding arousal would be similar, whether stimulated by added inspiratory resistive load, hypoxia, or hypercapnia. To test this hypothesis, we studied eight young, healthy men during full-night sleep studies. We measured their electroencephalography (EEG), electromyography (EMG), electrooculography (EOG), inspired ventilation (VI), end tidal PCO2 (PetCO2), O2 saturation, and esophageal pressure (esophageal balloon) while inducing arousal from non-REM sleep using (1) a 30-cm H2O/L/s added resistiv...

Extrapulmonary tuberculosis in the United States.

Abstract: From 1963 to 1986, the number of reported cases of pulmonary tuberculosis in the United States declined an average of 5.0% annually, and the number of cases of extrapulmonary tuberculosis declined an average of 0.9% annually over the same period. In 1986, 17.5% of all cases of tuberculosis were extrapulmonary. Of pulmonary cases, 63.0% occurred among racial ethnic minorities and the foreign-born, whereas of extrapulmonary cases, the respective proportion was 71.2%. After adjustment for other variables, the proportion of extrapulmonary tuberculosis among all patients with tuberculosis by age was found to be largest in children and generally to decrease with increasing age, larger among black, Asian, and American Indian than among non-Hispanic white patients, larger among female than among male patients, and larger among the foreign-born than among patients born in the United States. The smaller decline in extrapulmonary tuberculosis over the years may be partially due to changes in the demographic characte...

Relationship of lung function to severity of osteoporosis in women.

Abstract: To determine if the severity of osteoporosis and its resultant hyperkyphosis cause measurable impairment of lung function, 74 women referred for osteoporosis evaluation underwent pulmonary function testing. Women with thoracic wedge compression fractures secondary to osteoporosis had significantly lower percent predicted FVC than did those without fractures. In hierarchical regression analysis, after controlling for age and arm span, there was a significant effect on FVC of the degree of hyperkyphosis as measured by Cobb's angle (increment in R2 = 0.14, p less than 0.001). The addition of the number of vertebral fractures to the model was also significant (increment in R2 = 0.06, p less than 0.002), but cortical bone volume, bone mineral density, and smoking status did not significantly improve the model. From one half of subjects tested, a regression equation was generated relating %FVC and the number of thoracic fractures: %FVC = 103.4 - 9.4 x number of fractures. When used to predict lung function impairment in the second half of study subjects, the correlation between measured and %FVC was r = 0.59 (p less than 0.002). Kyphosis and thoracic compression fractures caused by osteoporosis produce modest but predictable declines in vital capacity in women.

Interstitial lung disease in polymyositis and dermatomyositis. Clinical features and prognosis as correlated with histologic findings.

Abstract: Open lung biopsies from 14 patients and autopsy tissue from one patient with polymyositis/dermatomyositis were reviewed in an attempt to correlate histologic features with clinical, radiographic, and prognostic variables. Three major groups based on histologic patterns were identified: bronchiolitis obliterans organizing pneumonia (BOOP), usual interstitial pneumonia (UIP), and diffuse alveolar damage (DAD). Patients with BOOP had a more favorable prognosis than did patients with UIP. Patients with DAD had a uniformly poor prognosis. One patient had a cellular interstitial pneumonia and did well. Histologic subclassification of the interstitial lung disease proved to be a better predictor of survival than did the radiographic appearance or the clinical presentation. These findings suggest that there is a broader range of histologic findings in polymyositis-dermatomyositis than is suggested in the literature and that subclassification may be useful for prognosis.

Plasma tumor necrosis factor in patients with septic shock. Mortality rate, incidence of adult respiratory distress syndrome, and effects of methylprednisolone administration

Abstract: We assayed serial plasma samples from 86 patients, who were enrolled in a prospective randomized trial of the effects of methylprednisolone (MPSS) in septic shock, for the presence of cytokine tumor necrosis factor (TNF) using an enzyme-linked immunosorbent assay. TNF was present in the plasma of 27 of the 74 patients with septic shock, but in only 1 of the 12 patients with shock due to other causes. TNF was detected with equal frequency in patients with shock from gram-negative or from gram-positive bacillary sepsis. TNF levels were highest on the initial sample and decreased significantly over the subsequent 24 h in both the patients treated with MPSS and in those given placebo. Patients with detectable TNF had a higher incidence and severity of the adult respiratory distress syndrome and a higher mortality rate than did patients without detectable TNF.

Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge

Abstract: Sulfidopeptide leukotrienes have been implicated in the pathogenesis of asthma because of their ability to induce bronchospasm, airways hyperreactivity, and increased mucus production. In the present study, the leukotrienes (LT) C4, D4, and E4 were measured in bronchoalveolar lavage fluid (BALF) before and 5 min after endobronchial allergen challenge in four subject groups: nonatopic nonasthmatic, nonatopic asthmatic, atopic nonasthmatic, and atopic asthmatic. As determined by high performance liquid chromatography (HPLC), after allergen challenge, the predominant sulfidopeptide leukotriene found in BALF from atopic asthmatics was LTC4. Smaller amounts of LTD4 and LTE4 were detectable. The baseline level of leukotrienes in the atopic asthmatics was 64 +/- 18 pg/ml, with measurable levels being found in nine of 11 samples. Atopic nonasthmatics had measurable levels in only one of seven baseline samples, whereas five of six nonatopic subjects had undetectable levels. Allergen challenge in atopic asthmatics resulted in significant increases in LTC4 over prechallenge levels (64 +/- 18 to 616 +/- 193 pg/ml) (p less than 0.01) and over levels in the three control groups after challenge (p = 0.0297). The atopic nonasthmatic group also had detectable leukotriene levels after allergen challenge (88 +/- 32 pg/ml), whereas leukotrienes remained undetectable in five of the six nonatopic samples. For comparison, histamine and the prostanoids prostaglandin D2 (PGD2) and thromboxane B2 (TxB2) were also measured in BALF. The levels of all three of these mediators increased in BALF from atopic asthmatics after allergen challenge. After allergen challenge, the best correlation was found between the levels in BALF for the prostanoids PGD2 and TxB2 (r = 0.88).(ABSTRACT TRUNCATED AT 250 WORDS)

Severe community-acquired pneumonia. Etiology, prognosis, and treatment.

Abstract: The frequency of community-acquired pneumonia coupled with its mortality rate of 10 to 25% is of growing concern to clinicians. A prospective study of 67 patients with severe community-acquired pneumonia was carried out to determine the causative agents, the impact fore-knowledge of the etiology has on the outcome, the value of clinical and radiologic criteria in predicting the evolution, and the efficacy of empirical therapy. The study group included 45 men and 22 women (mean age: 56.8 ± 16.6 yr), and 46.2% suffered from a concurrent debilitating disease. The cause of pneumonia was diagnosed in 32 cases, and the most common pathogens were Streptococcus pneumoniae (37.5%), Legionella pneumophila (21.8%), and gram-negative bacilli (25.0%). The fact that fungal infections were present in three patients and Pneumocystis carinii in one are worthy of note. The overall death rate was 20.8%. A fatal outcome was related to the age of the patient (p < 0.05), the presence of debilitating disease (p = 0.026), and se...

Airborne concentrations and particle size distribution of allergen derived from domestic cats (Felis domesticus). Measurements using cascade impactor, liquid impinger, and a two-site monoclonal antibody assay for Fel d I.

Abstract: The recent development of a sensitive two-site monoclonal antibody immunoassay for the major cat allergen (Fel d I) has made it possible to make accurate measurements of airborne cat allergen using low volume samplers that do not disturb the room. Houses with cats had from 2 to 20 ng Fel d I/m3 air compared with less than 0.2 ng/m3 in houses without cats. Using a cascade impactor and a multistage liquid impinger, the particle size distribution of airborne Fel d I in nine houses was 75% on particle greater than or equal to 5 microns in diameter and 25% (range, 10 to 62%) on particles less than or equal to 2.5 microns. In a cat vivarium with 12 cats, the air contained 40 ng Fel d I/m3, but less than 2% was detected on particles less than or equal to 2.5 microns. The air exchange rate in the vivarium (approximately 15 changes/h) appears to be the major difference from domestic houses (less than 0.5 changes/h). Repeated studies in one house confirmed a very high proportion (approximately 60%) of Fel d I on small particles. During domestic cleaning, the levels of small particle allergen in this house approached those produced by a nebulizer for bronchial provocation, i.e., 40 ng/m3. These results show unequivocally that significant airborne Fel d I is associated with small particles, which remain airborne for long periods. These findings are strikingly different from previous results obtained with airborne dust mite allergen. The results provide an explanation for the distinctive rapid onset of asthma or rhinitis in patients allergic to cats and a basis for designing a policy to reduce airborne allergen in houses with cats.

Adverse Effects of Large Tidal Volume and Low PEEP in Canine Acid Aspiration

Abstract: When normal lungs are ventilated with large tidal volumes (VT) and end-inspired pressures (Pei), surfactant is depleted and pulmonary edema develops. Both effects are diminished by positive end-expiratory pressure (PEEP). We reasoned that ventilatory with large VT-low PEEP would similarly increase edema following acute lung injury. To test this hypothesis, we ventilated dogs 1 h after hydrochloric acid (HCl) induced pulmonary edema with a large VT (30 ml/kg) and low PEEP (3 cm H2O) (large VT-low PEEP) and compared their results with dogs ventilated with a smaller VT (15 ml/kg) and 12 cm H2O PEEP (small VT-high PEEP). The small VT was the smallest that maintained eucapnia in our preparation; the large VT was chosen to match Pei and end-inspired lung volume. Pulmonary capillary wedge transmural pressure (Ppwtm) was kept at 8 mm Hg in both groups. Five hours after injury, the median lung wet weight to body weight ratio (WW/BW) was 25 g/kg higher in the large VT-low PEEP group than in the small VT-high PEEP group (p less than 0.05). Venous admixture (Qva/Qt) was similarly greater in the large VT-low PEEP group (49.8 versus 23.5%) (p less than 0.05). We conclude that small VT-high PEEP is a better mode of ventilating acute lung injury than large VT-low PEEP because edema accumulation is less and venous admixture is less. These advantages did not result from differences in Pei, end-inspiratory lung volume, or preload (Ppwtm).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical role of bronchoalveolar lavage in adults with pulmonary disease.

Abstract: BAL remains a powerful investigative tool In a short span of 20 yr, it has helped tremendously in understanding some of the aspects of the pathogenesis of diseases involving the lower respiratory tract To realize its full potential in the diagnosis and management of diseases involving the lower respiratory tract, there is a great need for standardization of the technical aspects of BAL as well as processing and analysis of the BAL cellular- and fluid-phase components Despite these hurdles, BAL has been found to be diagnostic in several infectious and noninfectious diseases involving the lower respiratory tract, and it provides valuable information that may be helpful in characterizing the prognosis and response to therapy in certain interstitial diseases of the lung It is expected that with future research, in particular long-term prospective epidemiologic and clinical studies in pneumoconioses and in other interstitial lung disease, BAL will prove more valuable in the diagnosis and management of such disease

Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage. The effects of antiasthmatic treatment with budesonide or terbutaline.

Abstract: We investigated the constituents of bronchoalveolar lavage (BAL) regarding cell profiles and released eosinophilic cationic protein (ECP) in 11 patients treated occasionally with inhaled bronchodilators (Group A) and 11 patients treated regularly with inhaled corticosteroids (Group B). A normal, healthy control group of 12 subjects was also recruited. Compared with Group A, Group B had a reduced recovery percentage of infused volume (p less than 0.05) and total cell number (p less than 0.01). Compared with the control group, there was a significant increase in the percentage of eosinophils (p less than 0.05) in both groups of asthmatics. In Group A there was also a significant increase in mast cells (p less than 0.05), serum-ECP (p less than 0.05), and BAL-ECP (p less than 0.001). No correlations between any of the cell variables and the level of airway responsiveness measured as PC20 histamine were found in any group. Group A patients were investigated twice--before and after 4 wk of randomly allocated treatment with either a regular beta-2-receptor agonist (terbutaline 250 micrograms, two puffs four times a day) or a regularly inhaled corticosteroid (budesonide 200 micrograms twice a day). The BAL differential cell counts were similar and not significantly affected by either treatment. However, BAL-ECP levels were decreased by budesonide treatment (p less than 0.05). ECP levels in serum and BAL were significantly correlated (p less than 0.05 to 0.001). The eosinophilic cell involvement in asthma is further emphasized by this study but the increase in numbers of eosinophils seems less important than their activity, here measured as release of one degranulation product, ECP. To suppress disease activity, repeated long-term treatment is important, but clear preference for either treatment cannot be given on the basis of our present results.

Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis. Use of the protected specimen brush technique in 54 mechanically ventilated patients.

Abstract: To obtain accurate information on distal bronchial microflora during acute exacerbation in patients with chronic bronchitis, we prospectively studied 54 such patients who had been receiving mechanical ventilation because of hypercapnic respiratory failure. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient within the first 24 h after admission. Cultures of protected brush specimens demonstrated no growth in 27 patients (50%). With the exception of fever (38.2 ± 0.8 versus 37.7 ± 0.6° C; p < 0.05), the initial severity of the episode of exacerbation was similar in patients with and without infection. A total of 44 organisms were isolated in the 27 patients with positive cultures; the predominant pathogens were Hemophilus spp. and Streptococcus spp. (involved in 74% of cases), but other organisms were isolated in 12 of 27 patients. Mortality rates, duration of mechanical ventilation, and duration of hospitalization were not significantly different between patients w...

The diagnosis of mild emphysema. Correlation of computed tomography and pathology scores.

Abstract: Early and accurate diagnosis of emphysema is said to be invaluable for identification of clinically silent and mild emphysema. Recently, computed tomography (CT) has been much advocated for its efficacy in detailed diagnosis of emphysema, and the results have been compared with the pathology grade of emphysema in resected lung specimens. To assess the ability of high resolution CT scan in detecting and grading mild emphysema, we correlated the high resolution CT scan with the pathology grade of emphysema and the destructive index (DI) of lung specimens from 42 patients undergoing thoracotomy for a solitary pulmonary nodule. The high resolution CT scan and the cut surface of the lung, corresponding exactly to the same plane of the CT scan image, were assessed using the picture-grading system of Thurlbeck and coworkers on a scale of zero to 100. The CT scores for all patients ranged from 12 to 57, with a mean +/- SD of 22.1 +/- 9.6 using 1-mm collimation (n = 35), and from 7 to 46 with a mean +/- SD of 16.5 +/- 8.3 using 5-mm collimation (n = 33). The pathology scores ranged from 10 to 57, with a mean +/- SD of 23.2 +/- 9.8 (n = 42). The DI ranged from 15.4 to 67.1, with a mean +/- SD of 31.4 +/- 10.8 (n = 42). The CT scores using 1-mm and 5-mm collimation correlated significantly with the pathology scores (r = 0.68 and 0.76, respectively, p less than 0.001), and with the DI (r = 0.62 and 0.74, respectively, p less than 0.001). The pathology scores correlated significantly with the DI (r = 0.72, p less than 0.001). We therefore concluded that high resolution CT can help to identify the presence and grading of mild emphysema.

Do patients with obstructive sleep apnea have thick necks

Abstract: During physical examination of patients with suspected obstructive sleep apnea (OSA), a comment is frequently made that they appear to have a short and fat neck. To confirm this subjective impression by objective measurements, we studied a group of 123 patients referred to us because of snoring and suspected OSA, all of whom had nocturnal polysomnography and measurements of external and internal neck circumference. The external neck circumference was measured at the level of the superior border of the cricothyroid cartilage. Internal neck circumferences were calculated from the measurements of pharyngeal, glottic, and tracheal areas obtained by the acoustic reflection technique. Internal pharyngeal circumference was further subdivided into the proximal, middle, and distal thirds. The acoustic technique also permitted us to measure the distance between the teeth and the glottic minimum, which reflects the length of the upper airway. Stepwise multiple linear regression analysis revealed that the apnea/hypopnea index (AHI) correlated only with the external neck circumference, the body mass index, and the internal circumference of the distal pharynx; these three variables accounted for 39% of the variability in AHI. We conclude that the external and internal neck circumferences and the degree of obesity are important predictors of sleep apnea; it is possible that obesity produces its effect via fat in the neck. We speculate that the static pharyngeal size modulated by the dynamic loading of the airway due to the weight of fatty tissue of the neck may contribute to the pathogenesis of OSA.

The Interrelationship among Bronchial Hyperresponsiveness, the Diagnosis of Asthma, and Asthma Symptoms

Abstract: Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community.

Pulmonary Infectious Complications of Human Immunodeficiency Virus Infection: Part I

Abstract: Introduction Diagnostic Approach History Physical Examination Laboratory Tests Chest Radiography Pulmonary Function Studies Radionuclide Imaging Sputum Examination Bronchoscopy Other Procedures Viral Infections Cytomegalovirus Infection Other Pulmonary Viral Infections Bacterial Infections Community-acquired Bacterial Pneumonias Nosocomial Bacterial Pneumonias Tuberculosis Mycobacterium avium Complex Other Mycobacterial Infections Fungal Infections Cryptococcosis Histoplasmosis Coccidioidomycosis Candidiasis Aspergillosis Other Fungal Infections Pneumocystis carinii Infection Taxonomy Epidemiology Pathology and Pathogenesis Clinical Features Diagnosis Treatment Adjunctive Measures Prevention Parasitic Infections Toxoplasmosis Cryptosporidiosis Strongyloidiasis Conclusion

The presence of airway reactivity before the development of asthma.

Abstract: Exaggerated airway reactivity is an essential component of the current asthmatic. It is not clear, however, if airway reactivity is genetically determined or acquired. To examine the possibility that increased bronchial reactivity exists prior to the development of asthma, we report on 20 subjects who were studied before and after the onset of clinical asthma. Subjects were part of a larger on-going study of the Natural History of Asthma. Thirteen subjects indicated by their answers to the National Heart, Lung, and Blood Institute respiratory questionnaire that they were not asthmatic at their initial visit. Seven subjects had pulmonary symptoms on their initial visit, but had not been diagnosed as asthmatic. Bronchial reactivity was assessed using a standardized methacholine challenge. For the 20 subjects, there was a mean interval of 3.5 yr between the initial visit and the diagnosis of asthma. Ten of 13 nonasthmatic subjects had moderate or strongly positive responses (208 breath units or less) to methacholine prior to onset of asthma. These 13 subjects were compared to age- and sex-matched controls, from both asthmatic and nonasthmatic families, who had not become asthmatic. There was a difference in bronchial responses at the initial visit between the 13 study subjects and their control subjects from nonasthmatic families, but not between the subjects and their controls from asthmatic families. Five of 7 subjects with pulmonary symptoms had responses of 100 breath units or less. Overall, 19 of 20 subjects had strongly positive responses to methacholine after the diagnosis of asthma was established. The results show that enhanced airway reactivity usually precedes the development of asthma, which could support a genetic basis for it.