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Spontaneous and induced sputum to measure indices of airway inflammation in asthma.

Inhalation of hypertonic saline to induce sputum may alter cells and fluid-phase markers in sputum. We have compared indices of inflammation in sputum produced spontaneously with sputum induced by an aerosol of hypertonic saline. Twenty-three asthmatics produced spontaneous followed by induced sputum on the same day. The sputum specimen was separated from saliva within 2 h, dispersed with dithiothreitol (DTT) and processed to obtain cytospins and supernatant. The statistical power to detect a 20% difference in sputum parameters was > 90%. Results are expressed as median and interquartile range [IQR]. Induced sputum had a higher proportion of viable cells (77.0 [19.0] versus 47.0 [38.0]%, p < 0.001), less squamous cell contamination (1.0 [1.2] versus 1.8 [34.0]%, p < 0.001) and better quality cytospins (score of 8.0 [4.0] versus 4.0 [2.0], p < 0.001). It also had lower fluid-phase levels of eosinophil cationic protein (ECP) (1,358 [1,102] versus 1,574 [2,479] microg/L) and fibrinogen (1,560.0 [3,130.0] versus 4,350.0 [5,970.0] ng/ml) but only the latter was significantly different (p = 0.02). Induced sputum was similar to spontaneous sputum in weight (200.0 [219.0] versus 270.0 [227.0] mg), total cell count (3.3 [4.1] versus 3.5 [4.5] x 10(6)/ml), proportion of nonsquamous cells, and levels of tryptase. The agreement between induced and spontaneous measurements was good, but fluid-phase levels were affected by the low viability of some spontaneous samples. We conclude that for the indices measured in asthmatic subjects, induced sputum separated from saliva is similar to lower respiratory secretions expectorated spontaneously and has the advantage of better cell viability.

Adult↗

Yield of computed tomography and bronchoscopy for the diagnosis of Mycobacterium avium complex pulmonary disease.

Mycobacterium avium complex (MAC) pulmonary disease with nodules and bronchiectasis is increasing. But the usefulness of computed tomography (CT) and bronchoscopy for diagnosis and the significance of MAC isolation from respiratory secretions are still unclear. For a 4-yr period, we prospectively examined the role of bronchoscopy with bronchial washing and transbronchial lung biopsy in 26 patients who had clusters of small nodules in the periphery of the lung associated with ectatic changes of the draining bronchi on the CT scan. None of them was infected with human immunodeficiency virus. Thirteen of the 26 patients (50%) had cultures positive for MAC, six in the sputum and 13 in the bronchial washing. Epithelioid granuloma was demonstrated in eight of 13 patients with culture-positive MAC and in two of 13 patients in whom MAC was culture-negative. Rapidly growing mycobacteria were cultured in the two patients. Seven of the eight biopsy-positive patients received treatment and responded by sputum conversion and/or radiographic improvement. We found that the CT finding was a useful clue to suspect MAC pulmonary disease and that the bronchial washing was more sensitive than the routine expectorated sputum for MAC isolation. Demonstration of granuloma in more than half of the MAC-positive patients would suggest that MAC may have invaded the lung tissue rather than colonized in the airways.

Adult↗

Bronchial artery embolization for the treatment of hemoptysis in patients with cystic fibrosis.

Hemoptysis is common in patients with cystic fibrosis (CF). Bleeding may vary in severity, ranging from minor blood-streaking of sputum to expectoration of significant quantities of blood. Major hemoptysis, defined as bleeding greater than 240 ml/24 h, represents a medical emergency. Bronchial artery embolization (BAE) is one of the treatment options for hemoptysis. We reviewed the 10-yr experience at the University of North Carolina Hospitals in the treatment of hemoptysis by BAE. Eighteen patients with CF were hospitalized on 29 occasions and underwent 36 BAE procedures for the control of hemoptysis. Most patients (n = 11) had very severe lung disease (FEV1 < 35%) with a high incidence (n = 9, 50%) of multi-drug-resistant bacteria. Fifteen patients (n = 33 procedures) were followed for a mean of approximately 22 mo after BAE. The overall efficacy of BAE for initial control of hemoptysis was 75% (n = 22) after one session, 89% (n = 26) after two sessions, and 93% (n = 27) after three sessions. The overall recurrence rate per episode was 46% (12/26 presentations in four patients) with a mean time for recurrence of approximately 12 mo. There was a high incidence (75%) of bleeding from nonbronchial systemic collateral vessels among patients (n = 7) who had undergone a previous BAE. There were two deaths associated with massive hemoptysis despite BAE. Three patients had transient neurologic deficits during BAE. We concluded that BAE is a relatively safe and effective means of treating significant hemoptysis in patients with CF.

Adolescent↗

Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation.

In uncontrolled studies, noninvasive positive pressure ventilation (NPPV) was found useful in avoiding endotracheal intubation in patients with acute respiratory failure (ARF) caused by severe community-acquired pneumonia (CAP). We conducted a prospective, randomized study comparing standard treatment plus NPPV delivered through a face mask to standard treatment alone in patients with severe CAP and ARF. Patients fitting the American Thoracic Society criteria for severe CAP were included in presence of ARF (refractory hypoxemia and/or hypercapnia with acidosis). Exclusion criteria were: severe hemodynamic instability, requirement for emergent cardiopulmonary resuscitation, home mechanical ventilation or oxygen long-term supplementation, concomitant severe disease with a low expectation of life, inability to expectorate or contraindications to the use of the mask. Fifty-six consecutive patients (28 in each arm) were enrolled, and the two groups were similar at study entry. The use of NPPV was well tolerated, safe, and associated with a significant reduction in respiratory rate, need for endotracheal intubation (21% versus 50%; p = 0.03), and duration of intensive care unit (ICU) stay (1.8 +/- 0.7 d versus 6 +/- 1.8 d; p = 0.04). The two groups had a similar intensity of nursing care workload, time interval from study entry to endotracheal intubation, duration of hospitalization, and hospital mortality. Among patients with chronic obstructive pulmonary disease (COPD), those randomized to NPPV had a lower intensity of nursing care workload (p = 0.04) and improved 2-mo survival (88.9% versus 37.5%; p = 0.05). We conclude that in selected patients with ARF caused by severe CAP, NPPV was associated with a significant reduction in the rate of endotracheal intubation and duration of ICU stay. A 2-mo survival advantage was seen in patients with COPD.

Acute Disease↗

Induced sputum cell counts in healthy adults.

Induced sputum cell counts provide a relatively noninvasive method to evaluate the presence, type, and degree of inflammation in the airways of the lungs. Their interpretation requires a knowledge of normal values from a healthy population. The objective was to examine the total and differential cell counts in induced sputum from a sample of healthy adults. A total of 118 healthy nonsmoking adults were studied. None had asthma or airflow obstruction (negative history, FEV(1) >/= 80% predicted, ratio of FEV(1) to vital capacity [FEV(1)/VC] >/= 80%, methacholine PC(20) >/= 16 mg/ml). Forty-six were atopic. Sputum induction produced an adequate sample in 96 subjects [53 males, mean age (range) 36 (18 to 60) yr]. The expectorate was processed within 2 h; sputum was selected, treated with dithiothreitol, filtered, and examined in a hemocytometer for total cell count and viability and on Wright-stained cytospins for a differential cell count. The mean, median (90th percentile) total cell count was 4.1, 2.4 (9.7) x 10(6) cells/g and cell viability was 69.6, 72.0 (89.7)%. The proportions of eosinophils were 0.4, 0.0 (1.1)%, neutrophils 37.5, 36.7 (64.0)%, macrophages 58.8, 60.8 (86.1)%, lymphocytes 1.0, 0.5 (2.6)%, metachromatic cells 0.0, 0.0 (0.04)%, and bronchial epithelial cells 1.6, 0.3 (4.4)%, respectively. Female gender and atopy were associated with a significant elevation of eosinophils; mean difference between male/female was 0.3% (p = 0.043) and between atopic/nonatopic 0.4% (p = 0.024). This study has identified reference values for total and differential cell counts in induced sputum of healthy adults.

Adolescent↗

Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma.

Although airway inflammation is recognized as a key feature of asthma, the characteristics of airway inflammation in children with acute severe asthma are not well defined. The aim of this study was to describe the characteristics of airway inflammation in children with an acute exacerbation of asthma using sputum cell counts and fluid-phase measurements and to examine the changes in these parameters upon resolution of the exacerbation. Children (n = 38) presenting to the Emergency Department with acute asthma underwent successful sputum induction using ultrasonically nebulized normal saline (n = 22), or expectorated sputum spontaneously (n = 16). Sputum induction was repeated at least 2 wk later when the children had recovered (n = 28). Sputum portions were selected, dispersed and total and differential cell counts performed. Neutrophil elastase and EG2-positive eosinophils were assessed and fluid-phase eosinophil cationic protein (ECP), myeloperoxidase (MPO), interleukin-8 (IL-8), and IL-5 were measured. During the acute exacerbation the median (range) total cell count was 8.4 x 10(6)/ml (0.5 to 190.3), and fell significantly at resolution to 1.3 x 10(6)/ml (p < 0.01). The inflammatory cell infiltrate was mixed and included eosinophils (0.8 x 10(6)/ml), neutrophils (3.3 x 10(6)/ml), and mast cells. EG2(+) cells were high and correlated with the degree of airflow obstruction (r = -0.5, p = 0.02). They decreased significantly at resolution as did supernatant ECP (1,078 versus 272 ng/ml), suggesting that eosinophils were activated during the exacerbation. MPO was 220 ng/ ml at exacerbation and fell significantly to 1 ng/ml at resolution. Levels of IL-8 and IL-5 were elevated during the acute exacerbation and IL-8 concentrations decreased at resolution. In conclusion, airway inflammation can be studied in children with acute asthma by sputum induction. Airway inflammation is present during an acute exacerbation of asthma, and is characterized by infiltration and activation of both eosinophils and neutrophils. The heterogeneity of airway inflammation in acute asthma may influence response to corticosteroid therapy.

Acute Disease↗

Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease.

Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB-HI, n = 10) and in patients with obstructive chronic bronchitis (COPD-HI, n = 10) by analyses of the sol phase of spontaneously expectorated sputum (SSP). As compared with the CB-HI group, the COPD-HI group had significantly higher (p < 0.05) levels of myeloperoxidase (MPO) and tumor necrosis factor (TNF)-alpha in their SSP, whereas the degree of plasma protein leakage (SSP-to-serum ratio of plasma proteins) and the levels of interleukin (IL)-8, secretory IgA, and lactoferrin were similar in the two groups. These findings point to differences in pathophysiology in CB-HI and COPD-HI. The high level of TNF-alpha in the SSP of COPD-HI patients is in accord with the proposed role of TNF-alpha in the development of airway obstruction in COPD patients. In apparent contradiction, low levels of TNF-alpha were found in the SSP of noninfected but otherwise similar COPD patients (n = 9). This finding, however, does not exclude an exaggerated TNF-alpha response to infection or another stimulus in the airways of COPD patients. The SSP levels of MPO and IL-8, and the degree of plasma protein leakage in the COPD-HI group, were retrospectively compared with and found significantly higher than those of noninfected COPD patients, suggesting a more marked inflammatory response in COPD-HI. Whether this reflects a direct cause-and-effect relationship should be addressed in a future long-term prospective study involving repeated measurements in the same patients.

Bronchitis↗

Protected transbronchial needle aspiration and protected specimen brush in the diagnosis of pneumonia.

Protected transbronchial needle aspiration (PTBNA) of pneumonic lung theoretically could bypass dislodged upper respiratory tract flora, a potential source of contamination of protected specimen brush (PSB) cultures. To evaluate the usefulness of PSB and PTBNA in establishing the etiology of pneumonia, we prospectively studied 20 patients with acute bacterial pneumonia not receiving antibiotics. After informed consent, patients had fiberoptic bronchoscopy under fluoroscopy to localize the pneumonia, and specimens were obtained by the PSB. The protective plug of a specially devised needle for PTBNA was pneumatically dislodged and aspiration was performed within the infiltrate under fluoroscopy. Quantitative cultures were plated immediately for aerobes, anaerobes, and Legionella. Greater than 4 X 10(3) organisms/brush or 1 X 10(4) organisms/ml needle aspirate were considered to be consistent with infection. The results using PSB and PTBNA were compared in 15 of 20 patients in whom a definitive diagnosis (positive blood or pleural fluid culture) or presumptive diagnosis (expectorated sputum culture, clinical characteristics, and response to specific therapy) was established. The PSB and PTBNA cultures on uninfected control subjects (n = 5) being bronchoscoped for other reasons were negative. The PSB and PTBNA were each diagnostic in 2 of the 5 patients with definitive diagnoses. In the group with a presumptive diagnosis (n = 10), PSB was diagnostic in 7 of 10 and PTBNA in 9 of 10. The overall (definitive plus presumptive) diagnostic yield was 60% for PSB and 73% for PTBNA. Multiple organisms were isolated in high concentrations in 53% of the patients. The most common organisms recovered in addition to the primary pathogen was alpha hemolytic streptococci.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinical features of adenosquamous lung carcinoma in 127 patients.

There has been increased recognition of adenosquamous lung carcinoma since the 1982 modification of World Health Organization (WHO) histologic criteria. However, data on clinical features of this histologic subtype were nonexistent. Medical records of 127 patients with adenosquamous lung carcinoma were reviewed to determine the clinical features, namely, age, race, sex, smoking history, asbestos exposure, symptoms present at the time of diagnosis, stage, treatments, and survival. The age distribution was: less than 40 yr, 3%; 40 to 49, 17%; 50 to 59, 28%; 60 to 69, 32%; 70 to 79, 18%; greater than or equal to 80, 2%. Men constituted 72%, and 90% were smokers. Four smokers had documented asbestos exposure. The symptoms in order of decreasing frequency were cough, weight loss, expectoration, anorexia, chest pain, dyspnea, weakness, hemoptysis, pneumonia, fever, nausea, vomiting, dizziness, and chills. Stage could be ascertained in 120 (95%) patients. Local stage constituted 10%, regional constituted 30%, and distant constituted 60%. Local stage had the best survival, with a projected 5-yr survival of 62%. Median survivals in regional and distant stages were 8 and 4 months, respectively. Symptoms of adenosquamous lung carcinoma were similar to other histologies. Most patients present in regional or distant stages. Local-stage patients had a good long-term survival after surgical excision of the tumor.

Adenocarcinoma↗

Allergic bronchopulmonary mycosis caused by Pseudallescheria boydii.

Two cases of allergic bronchopulmonary pseudallescheriosis (ABPP) are described. These are the first cases of this allergic bronchopulmonary mycosis (ABPM) reported in which the clinical and serologic criteria are described. The first case was in a patient with mild asthma, and it resolved spontaneously after expectoration of a mucous plug. The second was in a patient with recurrent allergic bronchopulmonary aspergillosis with an exacerbation of ABPM caused by Pseudallescheria boydii. The total serum IgE, IgG, and IgE antibodies against P. boydii and the clinical picture well define ABPP. This diagnosis may be important to recognize in order to prevent a progression of the patient's lung disease.

Adult↗

Chest physical therapy management of patients with cystic fibrosis. A meta-analysis.

The purpose of this overview is to quantitatively assess the conflicting body of literature concerning the efficacy of physical therapy modalities for clearing bronchial secretions in the treatment of patients with cystic fibrosis (CF). The modalities examined included positive expiratory pressure (PEP) mask, forced expiratory technique (FET), exercise (EX), autogenic drainage (AD), and standard physical therapy (STD), consisting of postural drainage, percussion, and vibration. Computerized searches of the MEDLINE and Cumulative Index for Nursing and Allied Health databases were performed for the years from 1966 to 1993. The authors of relevant papers were contacted for unpublished information. Studies were considered relevant if they met the following criteria: randomized trials in patients with a definite diagnosis of CF; an intervention of any combination of PEP, FET, STD, AD, or EX; and an outcome of FEV1, sputum weight, or sputum clearance. A review of 456 citations yielded 65 potentially relevant trials and 8 review articles; of these, 35 met the inclusion criteria and were incorporated into the overview. These studies evaluated different combinations of physical therapy modalities; therefore, we performed seven separate meta-analyses comparing the independent techniques using the pooled effect size technique. Standard physical therapy resulted in a significantly greater sputum expectoration than no treatment (effect size of 0.61 SD units, p < 0.0001). The combination of standard therapy with EX with associated with a statistically significant increase in FEV1 over STD alone (effect size of 0.48 SD units, p = 0.04). No other differences between physical therapy modalities were found.

Cystic Fibrosis↗

Fatal Neisseria (Branhamella) catarrhalis pneumonia in an immunodeficient host.

A 64-year-old man with far-advanced IgA multiple myeloma presented with fulminant and rapidly fatal bronchopneumonia. Gram stains of expectorated sputum and of transtracheal aspirate revealed gram-negative intracellular and extracellular diplococci. Cultures of these specimens yielded Neisseria catarrhalis. Subsequent histologic examination of the lung confirmed the presence of numerous gram-negative diplococci in the alveolar spaces. The pathogenic potential of this nasopharyngeal commensal is discussed in both the normal and the immunosuppressed host.

Bacteriological Techniques↗

A respiratory epidemiologic survey of grain mill workers in Cape Town, South Africa.

Exposure to grain dust may induce acute and chronic respiratory, nasal, and ocular symptoms. The prevalence of respiratory symptoms, atopic status, and lung function changes, as measured by pulmonary function tests (PFT) over the week in 582 grain mill workers and 153 control subjects not exposed to grain dust were studied in Cape Town. Atopic status, smoking habits, and baseline PFT did not differ significantly between grain workers and control subjects. Grain workers showed significant deterioration in lung function values over the week, with forced expiratory volume in one second declining on average by 4.8% compared with an increase of 3.3% in control subjects (p less than 0.001). Forced expiratory flow during the middle half of the forced vital capacity declined by 14.8% in grain workers and by 0.8% in control subjects (p less than 0.0001). Grain workers had significantly higher prevalences than did control subjects of regular cough (46 versus 30%), expectoration (35 versus 17%), wheeze (25 versus 11%), and watery eyes (25 versus 10%) (p less than 0.01 for all). These symptoms were not related to the duration of employment. A dose-response relationship, independent of smoking habits, was demonstrated between reported dust exposure and symptoms as well as between dust exposure and PFT. These results have important implications for the grain mill industry in South Africa where there is insufficient legislation and worker compensation.

Adult↗

Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function.

We have assessed the uniformity of regional ventilation during tidal breathing using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established.

Adult↗

Spinal cord stimulation: a new method to produce an effective cough in patients with spinal cord injury.

Patients with spinal cord injury have an increased risk of developing respiratory tract infections as the result of expiratory muscle paralysis and consequent inability to cough. We have developed a method by which the expiratory muscles can be activated via lower thoracic and upper lumbar spinal cord stimulation to produce an effective cough mechanism. In a tetraplegic patient who required frequent (8.57+/-2.3 times per week [mean+/-SEM]) caregiver assistance to facilitate airway clearance and expectoration of secretions, three epidural electrodes were applied in the T9, T11, and L1 spinal cord regions. During stimulation at the T9 and L1 levels, airway pressures were 90 and 82 cm H2O, respectively. Peak expiratory flow rates were 6.4 L/s and 5.0 L/s; respectively. During combined (T9+L1) stimulation, airway pressure and expiratory flow rate increased to 132 cm H2O and 7.4 L/s, respectively. Addition of the third lead did not result in further increases in pressure generation. These values are characteristic of those observed with a normal subject. Because the patient is able to trigger the device independently, he no longer requires caregiver support for airway management. If confirmed in additional patients, spinal cord stimulation may be a useful method to restore an effective cough mechanism in patients with spinal cord injury.

Cough↗

Studies on the role of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects.

These experiments were performed to determine the importance of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects. Cephalic stimulation was induced by a modified sham feeding (MSF) technique, during which subjects chewed and expectorated appetizing food. The response to MSF was compared with that to gastric distention with 600 ml NaCl, glucose, or food. In addition, we measured the extent to which cephalic stimulation augments acid secretion that has been stimulated simultaneously by these other mechanisms. Our conclusions are as follows: (a) cephalic stimulation accounts for approximately one-third of the acid secreted when all mechanisms act simultaneously (food-distention plus MSF); (b) within the limits imposed by the maximal secretory capacity, the response to MSF is approximately the same, regardless of whether acid secretion is otherwise unstimulated or is stimulated simultaneously by gastric distention with NaCl, glucose, or food; and (c) gastric distention prolongs the response to cephalic stimulation.

Adult↗

Pulmonary artery agenesis presenting as massive hemoptysis--a case report.

Massive hemoptysis is the expectoration of approximately 600 ml of blood in twenty-four hours. Major causes of massive hemoptysis are tuberculosis, bronchiectasis, pulmonary neoplasm, fungus ball, bronchial adenomas, lung abscess, intrabronchial rupture of an aortic aneurysm, cystic fibrosis, pulmonary infarction, and pulmonary trauma. Other, less common causes include Goodpasture's syndrome, broncholiths, pulmonary varix, A-V malformation, and bleeding disorders. Agenesis of the pulmonary artery usually occurs in association with congenital cardiac anomalies, and isolated unilateral absence of the pulmonary artery is uncommon. About 10% of the patients with pulmonary artery agenesis develop inconsequential hemoptysis, but massive hemoptysis is a very rare complication of this anomaly. The following is a case report of a twenty-nine-year-old man with agenesis of the left pulmonary artery, who presented with massive hemoptysis requiring embolization and, eventually, pneumonectomy.

Adult↗

Ultraviolet-fluorescence bronchoscopy in early detection of bronchogenic carcinoma.

The still unsatisfactory prognosis of bronchogenic carcinoma prompted the search for possibilities of better early and detailed diagnosis. This led us to the idea of UV-fluorescence bronchoscopy. The patient inhales 5 ml of an aqueous 5% solution of fluorescein, together with a beta2 stimulator, 10-15 minutes before the bronchoscopy, by means of a pressure inhaler. While the normal mucous membrane cleanses itself by virtue of ciliary action (secretions containing fluorescein are expectorated or drawn off during the bronchoscopy), carcinoma, carcinomatous lymphangiosis, superficial tumor infiltrations and nonciliated metaplasias are stained. These places fluoresce in UV light, even when they cannot be observed with the naked eye or with an optical system. In this way, they are made visible for directed biospy. Malignant changes not discernible by means of the methods hitherto employed can thus be diagnosed and sites determined with greater accuracy for proposed resection.

Bronchi↗