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The significance of bronchoscopy for the diagnosis of Mycobacterium avium complex (MAC) pulmonary disease.

To investigate the usefulness of bronchoscopy for the diagnosis of Mycobacterium avium complex (MAC) pulmonary disease, we retrospectively reviewed the clinical charts, and radiographic and bacteriologic findings of all patients who were admitted to our hospital between 1994 and 2000, and who fulfilled the 1997 American Thoracic Society (ATS) criteria for MAC pulmonary infection. A total of 132 patients were diagnosed as affected by MAC pulmonary disease during that period. Of these, bronchoscopic examination was performed in those patients who showed negative sputum smear for mycobacteria on three consecutive days (n = 43) or who could not expectorate sputum (n = 2). Of 42 patients, sputum culture was positive for MAC in 34 patients (81.0%). Bronchial washing sample was smear-positive for MAC in 17 of 39 patients (43.6%), and culture-positive for MAC in 33 of the 39 patients (84.6%). Transbronchial lung biopsy (TBLB) specimens revealed specific findings (epithelioid cell granuloma and/or acid-fast bacilli) in 14 of 38 patients (36.9%). Bronchial washing of all patients who showed specific histology in TBLB grew MAC in culture. Based on the bronchoscopic examination, we could diagnose MAC pulmonary disease in 36 patients. In addition, smear and polymerase chain reaction (PCR) results of bronchial washing made possible an early diagnosis of MAC pulmonary disease in 15 patients. We examined the relation of CT findings to bronchial washing results. Isolation of MAC in bronchial washing is significantly related to small nodular opacity around the ectatic bronchi on the CT scan (p = 0.016). In our retrospective study, in sputum smear-negative patients with MAC pulmonary disease, MAC isolation by culture of bronchial washing was no more frequent than that with sputum culture. However, bronchial washing is useful to differentiate infection from casual isolation of MAC. In addition, we could make early diagnosis of MAC pulmonary disease based on smear and PCR results of bronchial washing. To make a diagnosis of MAC, bronchial washing is superior to TBLB, and should be done in the bronchus which drains the area revealing small nodular opacity around ectatic bronchi.

Adult↗

Diagnostic strategies in Pneumocystis carinii pneumonia.

Pneumocystis carinii (P. carinii) remains a major pulmonary pathogen for the immunocompromised patient. In HIV infected patients, P. carinii represents the most commonly diagnosed cause of pneumonia. In the AIDS patient, empiric therapy based on clinical presentation has its proponents. However, this approach has been associated with a worse overall prognosis for the at risk patient. Because P. carinii can not be cultured, specific identification relies on examining respiratory specimens ranging from expectorated sputum to bronchoscopy with bronchoalveolar lavage (BAL). The low sensitivity of conventional stains has led to the search for antibodies to P. carinii and the use of immunofluorescent techniques. In addition, the polymerase chain reaction (PCR) is successfully being used in the diagnosis of P. carinii. Overall, these techniques allow the clinician to tailor the diagnostic testing for the individual patient.

Acquired Immunodeficiency Syndrome↗

Effects of time after infection, mosquito genotype, and infectious viral dose on the dynamics of Culex tarsalis vector competence for western equine encephalomyelitis virus.

The vector competence of Culex tarsalis Coquillett for the BFS 1703 strain of western equine encephalomyelitis virus (WEEV) changed significantly as a function of time after infection, mosquito genotype, and infectious virus dose. After ingesting a high virus dose (5 log10 plaque-forming units [PFU]/0.1 ml), female of the susceptible high virus producer (HVP) strain rapidly amplified the virus, developed a disseminated infection, and efficiently transmitted WEEV by 4 days postinfection (dpi). The quantity of virus expectorated peaked at 4 dpi (mean 3.4 log10 PFU), and the percentage of females transmitting per os peaked at 7 dpi (80%); both measures of transmission subsequently decreased to low levels throughout the remainder of infected life. HVP females imbibing a low virus dose (3 log10 PFU/0.1 ml) were infected less frequently and took longer to amplify virus to levels recorded for the high virus dose group and did not transmit virus efficiently, thereby indicating midgut infection and escape barriers were dose and time dependent. These data emphasized the importance of elevated avian viremias in Cx. tarsalis vector competence. Females from the WEEV-resistant (WR) strain and two wild-type strains from Kern and Riverside counties were significantly less susceptible to infection at both high and low doses than was the HVP strain. Overall, females with a high virus titer more frequently had a disseminated infection, but there did not seem to be a distinct threshold demarcating this relationship. In marked contrast, all infected females transmitting virus had body titers >4.3 log10 PFU, and most had titers >4.8 log10 PFU. These data indicated that not all females with a disseminated infection transmitted virus because of the presence of one or more salivary gland barriers.

Animals↗

Tracheopathia chondro-osteoplastica. A clinical study of thirty cases.

During the last 12 years, 30 cases of tracheopathia chondro-osteoplastica have been diagnosed at the Department of Otolaryngology of Kuopio University. Ten of these were accidentally revealed by bronchoscopy, 2 by autopsy, but 18 were revealed through a systematic examination. Ten of these 18 were preliminarily diagnosed by indirect laryngoscopy. The average age for women was 51 and for men 42, the youngest patient being 11 and the oldest 71 years of age. The characteristic symptoms were long-term recurrent cough, hoarseness and periodic expectoration. The sputum was frequently abundant and crusty, and sometimes contained streaks of blood. Shortness of breath was a common symptom, but there were often entirely asymptomatic periods. The disease begins with a persistent purulent tracheitis, which, probably owing to calciphylaxis, causes accumulation of calcium salts in the tracheal mucosa. Cartilage and bone later develop around these accumulations. In most of the cases of tracheopathia chondro-osteoplastica in the present series, the condition was associated with atrophic rhinitis or pharyngitis. As the nasal disease improves, some regression may occur, though hardly healing. Calcium and phosphorus metabolism was not disturbed, and no immunological aberrations were found in any of the patients in this series.

Adolescent↗

Epidermal growth factor EGF in human saliva: effect of age, sex, race, pregnancy and sialogogue.

Saliva samples were obtained from volunteers either by spontaneous expectoration or after stimulation with citric acid (5%) and EGF was measured by a homologous radioimmunoassay. The mean +/- SEM of salivary human epidermal growth factor (hEGF) concentration in 70 males (aged 19-41) was 368.71 +/- 28.55 pmol/1 and 417.67 +/- 37.61 pmol/1 in 55 females (aged 19-45), P0.5. Values were found undetectable (32 pmol/1 in 6 prepubertal children. There was a tendency for hEGF to rise with age from about middle age but no significant racial or pregnancy related changes were observed. Stimulated sallivation with citric acid caused a fall in hEGF through a dilution effect. These results show that age has an important influence on the hEGF concentration of resting saliva.

Age Factors↗

Human respiratory mucous glycoproteins.

Biochemical characterization of human respiratory mucus has generally utilized expectorated specimens. In order to exclude extraneous contaminants in the analysis of airway glycoproteins, human airways were cultured and the mucous glycoprotein released into the supernatant analyzed. By incorporating 3H-labeled glucosamine or 14C-threonine into the media, the airways biosynthetically labeled the mucous glycoproteins (MGP), facilitating their analysis. The MGP chromatograph by gel filtration on Sepharose 2B in two fractions: one excluded from the column and one that enters the column. However, employing a gel filtration column with the ability to fractionate larger molecules, Sephacryl S-1000, it was found that MGP fractionate over a large range in molecular sizes and do not segregate into distinct fractions. The diffuse, broad peak of MGP fractionation on Sephacryl S-1000 is not affected by reduction and alkylation or by chromatography in 1 M NaCl. The fractionated MGP from Sepharose 2B were divided into larger and smaller molecular species, and their charge characteristics were determined by DEAE chromatography and preparative isoelectric focussing. MGP exhibit strong acidic charge characteristics that are uniform, as reflected in elution from DEAE and a single, sharp isoelectric focussing point. Enzymatic cleavage of the oligosaccharide side chains from MGP liberates more than 70% of the radiolabeled side chains. The side chains enzymatically cleaved from the larger and smaller molecular species of MGP are similar in size. Highly purified MGP were found to be 73% carbohydrate and 27% protein. Thus, human airways release a family of MGP that express marked heterogeneity in size but a uniform, strong acid charge and include side chains of similar size.

Carbohydrate Metabolism↗

Density gradient study of bronchial mucus aspirates from healthy volunteers (smokers and nonsmokers) and from patients with tracheostomy.

Because it is difficult to obtain, little is known of bronchial mucus from the normal human airway; it has been mainly studied as sputum expectorated in chronic bronchitis with particular attention to epithelial glycoprotein. We have now applied density gradient methods to study this and other macromolecules and lipids in normal airway mucus. After lavage at bronchoscopy, mucus was aspirated from six normal volunteers, that include one light and two heavy smokers. This normal mucus has been compared with that obtained from four patients with tracheostomy because of respiratory muscle paralysis due to neurological disease. The normal aspirates contained small threads of mucus, the tracheostomy aspirates viscous blobs of jelly, a difference in physical appearance reflected in macromolecular yields, 0.3-1 mg/ml and 6-24 mg/ml respectively. On analytical ultracentrifugation normal mucus showed no discernible material in the buoyant density region typical of epithelial glycoprotein (1.5 g/ml): Virtually all the material migrated to the miniscus and was predominantly lipids and proteins. A trace amount of material recovered from a higher density region (greater than or equal to 1.6 g/ml) was found to contain both glycoprotein and proteoglycan. Aspirates from the heavy smokers contained appreciable amounts of material with typical buoyant density (approximately 1.5 g/ml) but still with features of proteoglycan. In contrast in tracheostomy aspirates epithelial glycoprotein of typical buoyant density and chemical composition accounted for up to 25% of nondialyzable material. We conclude that under normal conditions typical epithelial glycoprotein is virtually absent from airway mucus and that the glycoconjugate present has features of glycoprotein and proteoglycan.

Adult↗

Deposition and clearance in large and small airways in chronic bronchitis.

Tracheobronchial clearance was studied twice in 16 patients with chronic obstructive bronchitis after inhalation of 6 microns (aerodynamic diameter) monodisperse Teflon particles labeled with 111In. At one exposure the particles were inhaled at an extremely slow flow, 0.05 L/s; at the other they were inhaled at a normal flow, 0.5 L/s. Theoretical calculations and experimental data in healthy subjects indicate particle deposition mainly in the smallest ciliated airways using 0.05 L/s, i.e., in the bronchiolar region, and an enhanced deposition in larger airways using 0.5 L/s. Lung retention was measured at 0, 24, 48 and 72 h. Clearance was significantly every 24 h for both exposures (p < .05). The fractions of retained particles were significantly larger for particles inhaled at 0.05 L/s compared to 0.5 L/s at all points of time (p < .001). Compared to healthy subjects, the retained fractions of deposited particles were larger in patients with bronchitis breathing at 0.05 L/s, but smaller with breathing at 0.5 L/s (p < .01). Significant relationships were found between lung retentions and airway resistance (Raw) at 0.5 L/s, r = -.68 (p < .01), but not at 0.05 L/s, and between lung retention at 24 h and weight of expectorated sputum at 0.05 L/s, r = -.50 (p < .05). There was, furthermore, an almost significant relationship between sputum volume and rate of tracheobronchial clearance between 0 and 24 h (in percentage of the total amount cleared during 72 h) at 0.05 L/s, r = .42 (p = .05). The results indicate that in patients with chronic bronchitis overall clearance of particles in small airways is incomplete, as compared to larger airways. An increased amount of mucus, however, seemed to improve clearance of peripherally deposited particles, possibly by making cough more effective in small airways.

Adult↗

Cell incohesiveness and pattern of extension in a rare case of bronchioloalveolar carcinoma.

A unique case of adenocarcinoma of the lung that showed aerogenous extension is presented. Although the primary focus was the usual invasive bronchioloalveolar carcinoma, the tumor cells were dissociated, floating and filling the alveolar spaces, the bronchioli, and the small bronchi at the periphery of the primary tumor and in every involved area in other lobes of the lung. Massive tumor cells were expectorated in coincidence with the appearance of abnormal densities on chest X-ray films. Ultrastructurally the dissociated tumor cells had numerous microvilli on the cell surface and rarely showed intercellular junctions. The tumor cells also contained well-developed rough and smooth endoplasmic membranes, crista-vesicular-type mitochondria, electron-dense granules, and granules with myelinlike figures. No mucous granules and no Clara-cell-type secretory granules nor lamellar bodies of the type seen in normal granular pneumocytes were seen. From these findings, it was concluded that the tumor cells in this case were rather poorly differentiated but somewhat resembled the hyperplastic cuboidal alveolar cells seen in the damaged lung and that they proliferated freely in airways, presenting aerogenous metastases. The biologic behavior of this tumor might be partly explained by the incohesive nature of the tumor cells.

Adenocarcinoma↗

Asthma: the yoga perspective. Part II: Yoga therapy in the treatment of asthma.

The integral yoga approach to asthma (and other psychosomatic disorders) is briefly outlined as meeting all of the requirements for an optimal, holistic, somatopsychic therapy (as outlined in Part I), including correction of distorted posture and faulty breathing habits, teaching a system of general muscle relaxation, techniques for the release of suppressed emotion and for reducing anxiety and self-conscious awareness, as well as special methods for the expectoration of mucus. Yoga practices are described in detail and the available psychophysiological research on yoga practice, as well as clinical-therapeutic studies on yoga as asthmatic therapy, are reviewed. It can therefore be concluded that yoga therapy is most effective with asthma.

Asthma↗

Spanish primary healthcare physicians' knowledge of resistance of respiratory germs and antimicrobial treatment in acute bronchitis.

OBJECTIVES: To determine what Spanish primary healthcare physicians consider the rates of pneumococcal resistance to be, the type of antimicrobial treatment they would prescribe on suspicion of high resistance and ascertain in which cases of acute bronchitis these physicians would initiate antibiotic treatment. METHODS: A cross-sectional, observational study was performed with a questionnaire distributed to 1368 physicians on their opinion on the degree of resistance of pneumococci to penicillins and macrolides in Spain. They were also asked which treatment they would recommend in penicillin-resistant pneumococcal infection and to indicate their degree of agreement regarding the use of antibiotics in different clinical situations of acute bronchitis. RESULTS: 843 physicians completed and returned the questionnaire, a response rate of 59.1%. Of the 750 physicians who answered the question concerning pneumococcal resistance, 312 stated resistance to be >30% (41.6%) while only 90 felt it to be <15% (12%). 153 physicians reported resistance to macrolides to be >30% (23%). In cases with suspicion of penicillin-resistant pneumococci, the clinicians stated they would prescribe quinolones (321, 40.3%) and macrolides (251, 31.5%). Of the 784 physicians who answered the questions on bronchitis, 662 preferred antibiotic therapy in acute bronchitis with purulent sputum (84.6%), 610 on uncertain diagnosis (77.8%), 569 in patients with fever over 38 degrees C (72.6%) and 210 on patient request (26.8%). CONCLUSION: Primary healthcare physicians in Spain are more concerned about pneumococcal resistance to penicillins than to macrolides although 35% of the strains isolated are resistant to the latter while only 10% are resistant to aminopenicillins. Furthermore, many physicians believe macrolides to be effective against pneumococcal infections. Despite their lack of efficacy in the treatment of acute bronchitis, many physicians prescribe antibiotics, mainly in cases with purulent expectoration, thus justifying the high consumption of antimicrobial agents in this disease.

Bronchitis↗

Respiratory tract inflammation in swine confinement workers studied using induced sputum and exhaled nitric oxide.

OBJECTIVE: To further define the asthma-like syndrome seen in swine confinement workers. DESIGN: A cross-sectional study was performed at a swine confinement facility in rural Nebraska and at the University of Nebraska Medical Center, Omaha, Nebraska. PARTICIPANTS: 24 swine confinement workers and 14 urban normal control subjects. All subjects completed a questionnaire concerning respiratory complaints. We performed hypertonic saline challenges on the swine confinement workers and control subjects in order to induce expectoration of sputum. Cell counts and cell differentials were determined in the induced sputum samples. Nasal, mean, and peak exhaled nitric oxide was measured in both groups. Spirometry was also done. RESULTS: Swine confinement workers were significantly more likely to report wheezing, cough, and sinusitis symptoms than controls (p = .003). Macrophages were significantly elevated in the induced sputum samples of the swine confinement workers vs the control subjects (0.59 macrophages/mL +/- 0.1 SEM vs 0.36 +/- .16; p = .006), while there was no difference in numbers of neutrophils. No eosinophils were observed. A small elevation in mean exhaled nitric oxide was seen in the swine confinement workers compared to normal controls (11.7 ppb +/- 0.6 SEM vs 10.2 +/- 1.6; p = 0.023). Spirometry values did not differ statistically between swine confinement workers and the control group. CONCLUSIONS: Swine confinement workers have signs and symptoms of lower respiratory tract inflammation when studied using induced sputum and exhaled nitric oxide. Findings in the swine confinement workers differ from those in asthmatics and chronic bronchitis.

Adult↗

Incidence of Legionella pneumophila in acute lower respiratory tract infections.

The etiological role of Legionella pneumophila and other infectious agents in acute lower respiratory tract infections in 112 patients attending an infectious disease clinic was estimated by a serological study of paired sera and bacteriological culture of nasopharynx swabs and culture and immunoelectroosmophoresis of expectorates. Only 2 of the patients had a 4-fold rise in antibody titre to L. pneumophila, suggesting a similar incidence of legionnaires' disease as reported from USA.

Adolescent↗

[Characteristics of clinical asthma types in elderly patients with bronchial asthma].

Asthma was classified into four types, Ia-1 (bronchospasm with 0-49 ml/day of expectoration), Ia-2 (with 5-99 ml/day), Ib (over 100 ml/day) and II (bronchiolar obstruction), according to clinical symptoms. Characteristics of airway responses in each clinical asthma type were compared between 25 elderly (mean age, 65.2 years) and 30 younger subjects (mean age, 44.9 years) with bronchial asthma, by observing ventilatory function and cellular composition in bronchoalveolar lavage (BAL) fluid. 1. In patients with types 1a-2 and Ib, the %V25 value was significantly lower in the elderly subjects than in the younger subjects. 2. Comparing the values of ventilatory parameters of type Ia-1 cases with other asthma types, %V25 value was lower in other asthma types than in type Ia-1 in the elderly. All ventilatory parameters examined were generally lower in type II cases than in other asthma types in the elderly, but this difference was not significant. In contract, in the younger subjects, the values of %MMF, %V50 and %V25 were significantly lower in type II cases than in other asthma types. 3. The proportion of neutrophils in bronchoalveolar lavage (BAL) fluid was higher in the younger patients with type II than in the elderly patients with the same type, although there was no significant difference between older and younger subjects. The proportion of BAL eosinophils in patients with type Ib was significantly higher in younger subjects than in elderly subjects. These results indicate that airway responses which are characteristic of each asthma type are stronger in younger patients than in elderly patients.

Aged↗

Viscoelastic properties of bronchorrhoea sputum in bronchial asthmatics.

Dynamic viscoelastic properties of 13 bronchorrhoea sputum samples from asthmatics with bronchorrhoea, defined as the production of watery sputum of 100 ml or more per day during asthmatic attacks, were examined and then compared with 7 saliva and 12 mucoid sputum samples obtained from patients during remission. Dynamic viscosity (eta') and elasticity (G') of bronchorrhoea sputum increased rapidly with time up to 2 hours after collection and slowly thereafter, whereas eta' and G' of saliva and mucoid sputum remained unchanged up to 6 hours after collection. Then, eta' and G' of saliva, bronchorrhoea and mucoid sputum samples were measured between 2 to 4 hours after expectoration. Bronchorrhoea sputum samples showed significantly larger values at frequencies of both 0.1 and 1.0 rad/sec than did saliva samples and also significantly smaller values than did mucoid sputum samples. Thus, bronchorrhoea sputum differed in dynamic viscoelastic properties from saliva, indicating that it does not result from hypersalivation. Based on data of viscoelastic changes with time, it can be assumed that the viscoelasticity of bronchorrhoea sputum in the airways is considerably less than the optimal range reported previously for mucociliary velocity, suggesting the possibility of impaired mucociliary transport.

Adult↗

A case of pulmonary Microsporidiasis in an acute myeloblastic leukemia (AML) - M3 patient.

Reported here is a case of microsporidiasis that occurred in an acute myeloblastic leukemia (AML)-M3 patient who underwent chemotherapy. Fever, cough, expectorate and dyspnea were observed during the therapy. Since this case was considered as adult respiratory distress syndrome due to the chest X-ray and arterial blood gas findings, the male patient was bounded to a mechanical ventilator. As coagulation tests showed compatible findings with disseminate intravascular coagulation (DIC), it was thought to be a case of sepsis originating from the lungs and DIC. Pseudomonas aeruginosa and Staphylococcus aureus were found in the sputum of the patient. Although he was given combined antibiotic therapy, there was no reduction in the fever. A bronchoalveolar lavage (BAL) sample was taken and Microsporidia sp. was found upon staining with Giemsa. The patient died due to sepsis and DIC just before receiving therapy for microsporidiasis. Pulmonary infection with Microsporidia, although classically occurring in patients with HIV infection, may occur rarely in leukemia patients, especially if previously treated with systemic immune suppression. This case reinforces the need to consider Microsporidia as a possible pathogen in immunocompromised patients with pulmonary infections.

Diagnostic Errors↗

[Asymptomatic infection of Legionella pneumophila in four cases with pulmonary diseases].

In view of the wide-spread existence of legionellae in cooling-tower and other environmental water, asymptomatic infection of this organism could occur. In order to verify the possibility of colonization of legionellae at lower respiratory tract of patients with various pulmonary diseases, a total of 22,036 sputum samples from in- and out-patients at National Sanyoso Hospital were examined during a five-year period from September, 1984 to August, 1989. Four (0.073%) out of 5,502 cases were culture-positive for L. pneumophila. L. pneumophila strains were isolated from expectorated, subsequently washed sputum samples of two male and two female patients with respiratory tract diseases. The identification of the isolates was genetically confirmed by the fluorometric microplate DNA-DNA hybridization method. The serogroup (SG) and viable counts of L. pneumophila per ml of sputum of each patient were as follows: 73 y/o female K.H., SG-6, 10(3) CFU; 75 y/o male H.J., SG-5, 10(4) CFU; 61 y/o female M.S., SG-5, 10(5) CFU; and 77 y/o male M.G., not-agglutinable against SG-1-6 antisera, 10(4) CFU. None of the four patients was clinically suspected of legionellosis and antibody titer of paired sera remained 1:64 or lower than 1:32. From these findings, we concluded that L. pneumophila can cause, though quite rarely, asymptomatic infection in human respiratory tract. None of the environmental samples obtained from in- and out-side of the Hospital was culture-positive for legionellae. Thus, the source of infection has remained unknown.

Aged↗

Severe pneumonia. When and why to hospitalize.

Relatively simple objective criteria are now available to predict which patients are at risk for bad outcomes from community-acquired pneumonia. In general, these include older patients and those with certain coexisting illnesses (especially neoplastic disease) or findings of altered mental status, hypotension, severe tachycardia, tachypnea, fever, acidemia, azotemia, hypoxemia, hyperglycemia, anemia, or hyponatremia. The major causes of severe pneumonia are S pneumoniae, H influenzae, and L pneumophila. Less common causes include mixed aerobic and anaerobic mouth flora, as well as M pneumoniae, C pneumoniae, gram-negative bacilli, and S aureus. Specific diagnosis is hampered by a lack of reliable diagnostic tests, but Gram's stain of expectorated sputum and cultures of sputum and blood may occasionally be helpful. Many empirical treatment regimens have been recommended, including those of the American Thoracic Society and the Infectious Diseases Society of America, which are reviewed here. It is hoped that better diagnostic tools will permit future targeting of microbes with narrow-spectrum therapy to diminish the risk of selection of resistant strains with empirical regimens.

Hospitalization↗