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Infectious pneumonias: a review.

Diplococcus pneumoniae remains the most frequent cause of community-acquired bacterial pneumonia. Other frequently isolated bacterial pathogens are Hemophilus influenzae, Klebsiella organisms, and Staphylococcus aureus. The etiologic agents most commonly implicated in hopsital-acquired pneumonias are gram-negative bacilli including E. coli, proteus organisms, and species of Klebsiella-Enterobacter, pseudomonas, and Serratia. Among older children and young-adults, Myocoplasma pneumoniae is a common cause of penumonia. Influenza is the most important cause of viral pneumonia in adults, but there is increasing concern about pulmonary infection due to adenoviruses. In those with a history of travel to endemic areas, the diagnosis of fungal pneumonia due to Histoplasma capsulatrum, Blastomyces dermatitides, or Coccidioides immitis, should be considered. Penumonias due to opportunistic fungi (including species of Candida, Aspergillus, and Phycomycetes) and higher bacteria such as Nocardia asteroides are also on the increase, and these arise mostly in compromised hosts. Treatment of pneumonia almost always must be started before culture results are known and in the overwhelming majority of cases, appropriate regimens can be selected after taking an adquate history, doing a careful physical examination, evaluating expectorated sputum for cells and organisms, and examining the chest x-ray. Although anti-infective agents are the mainstay of treatment for most infectious pneumonias, supportive therapy, including adequate tracheobronchial toilet, drainage of abscesses, oxygen inhalation, maintenance of adequate nutrition, and monitoring for super-infection and anti-infective side effects may be life-saving in certain situations.

Anti-Bacterial Agents↗

Lack of detectable DNA alkylation for bromhexine in man.

It is known that in vitro incubation of the expectorant drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) with nitrite yields methylcyclohexyl nitrosamine (NMCA). NMCA is capable of methylating DNA when administered to rats. In vivo tests with bromhexine have also demonstrated that the drug methylates DNA when it is orally administered in the presence of sodium nitrite, presumably due to the intragastric formation of NMCA. In this study the potential of bromhexine to methylate nucleic acids in man, under physiological conditions, has been investigated. 20 volunteers were orally administered on each of three successive days 48 mg of bromhexine hydrochloride, labelled with three deuterium atoms in the N-methyl group. Urine was collected before treatment and subsequent to the last dose, and analysed by GC-MS for d0- and d3-7-methylguanine. 7-Methylguanine is naturally occurring in urine owing to the turnover of t-RNA of which it is a minor constituent. It is also a repair product from nucleic acids methylated by carcinogens, which is known to be excreted unmetabolised largely within 24 h of the methylation process. Unlabelled 7-methylguanine was present at levels of 7.36 +/- 2.43 mg/d in control urine and 6.12 +/- 2.36 mg/d in treated urine, in accord with previously published values. The excretion of isotopically labelled 7-methylguanine averaged 0.43 +/- 0.077% of the unlabelled concentration for control urines and 0.44 +/- 0.066% for treated urines, i.e. no d3-7-methylguanine could be detected following the drug treatment. The observed signals were largely accounted for by the naturally occurring isotopes 13C and 15N.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The role of chronic bronchitis in the pathogenesis of chronic obstructive pulmonary disease.

Emphysema and a variety of lesions directly involving the conducting airways constitute the morphologic basis of air-flow obstruction in chronic obstructive pulmonary disease (COPD). Traditionally, inflammation and hypertrophy of the mucus-secreting elements within the central airways (chronic bronchitis), manifest clinically by chronic cough and recurrent bouts of purulent sputum expectoration due to infection, were held to be important in the development of COPD. While chronic cough and purulent bronchitis contribute to the morbidity associated with established COPD, epidemiologic studies suggest that neither is an independent factor in its causation. Furthermore, structure-function studies indicate that lesions in the distal bronchial tree (peripheral airways disease) are functionally more important than central airways disease in the genesis of air-flow obstruction. The severity of peripheral airways increases with advancing age, but it is only weakly related to the history of cigarette use. Other causes of peripheral airways disease have not been clearly elucidated, but a role for viruses, and certain other infectious agents, has been suggested by experimental animal studies.

Animals↗

[Reexpansion pulmonary edema after pneumothorax. Apropos of a case. Review of the literature].

Pulmonary edema after re-expansion of a pneumothorax occurs within a maximum of 3 days of the pneumothorax and manifests by intense clinical signs (cough, abundant foamy expectoration, major cyanosis), marked hypoxia and a "white lung" radiologic image. The outcome was rapidly favorable in the case reported, despite the severity of the initial symptomatology. Currently accepted physiopathologic mechanisms implicate numerous factors in the genesis of edema due to re-expansion. The lesional pulmonary edema can be explained by alteration in alveolar capillary permeability, by the atelectasis, hypoperfusion and stretching during revascularization, and possibly by the action of free radicals. A hemodynamic edema also exists as a consequence of the reduction in pulmonary interstitial pressure. Possible prophylactic measures are discussed, the most appropriate appearing to be very progressive evacuation of the pneumothorax.

Adult↗

[Invasive pulmonary aspergillosis].

Invasive pulmonary aspergillosis is an opportunistic pneumonia which is particularly common in immuno-depressed subjects. The most frequent risk factors are the intensity and duration of leucopaenia, cytotoxic drugs and steroid therapy. In the respiratory tract, the proliferation of Aspergillus fumigatus becomes possible when there is a failure of the reticulo-endothelial system and of the polymorphonuclear leucocytes. There is no typical clinical picture: one sees an acute febrile pneumonia resistant to antibiotics. However, the radiological signs are more suggestive with nodules and bilateral infiltrates with a tendency to cavity formation and sequestration. The prognosis is clinically linked to the rapidity of diagnosis. Broncho-alveolar lavage offers a new and non-invasive diagnostic method to search for Aspergillus mycelia or specific antigens. A direct examination and culture of sputum expectoration are both insensitive and non-specific but remain useful in some patients with leukaemia in a phase of agranulocytosis. Treatment rests on Amphotericin B taken orally.

Acute Disease↗

[Bronchial superinfection. Clinical trial of clavulanic acid-amoxicillin against josamycin].

Authors report a prospective clinical an bacteriological study in 32 patients, almost with a chronic bronchopulmonary disease. A group of 16 patients was treated with the association clavulanic acid-amoxicillin (ACA) and the 16 others with josamycin (J) for an acute exacerbation of bronchitis. Pus and numeration of bacteria in expectorations were the criteria of efficacity. Better results of ACA group were assessed with 14 cures (87%) against 4 (25%) (p less than 0.001) and no failure against 4 in J group (p less than 0.05). They conclude therapy with ACA is more effective and recommended in serious acute exacerbations in chronic bronchopulmonary diseases.

Aged↗

[Inflammatory mechanisms of bronchial asthma].

The definition of asthma brings with it the idea of inflammation, as bronchial obstruction, which characterises it, is associated with bronchospasm, hypersecretion and oedema. In the asthmatic, awareness of the bronchial inflammation at the time of diagnosis is essential, as it contributes to prognosis and therapeutic orientation. The diagnosis of bronchial inflammation begins with the clinical assessment, such as cough, expectoration and the worsening of symptoms in the morning alerts the clinician. In the course of certain clinical forms of asthma the absence of any relief of airflow obstruction by bronchodilators, although it is proved to be reversible after a few days of glucocorticoids, is evidence of inflammation. Fibreoptic bronchoscopy extends the clinical examination and enables a direct observation of airways inflammation. In addition it allows sampling, such as bronchial biopsy and/or broncho-alveolar lavage. The mechanism of bronchial inflammation are well understood; some mastocytes (mucous) are present in the broncho-alveolar contents and are probably the origin of inflammatory reaction, whether the stimulus be allergenic or not. The mediators liberated lead in part to the bronchial obstruction but equally to cellular recruitment and thus to an amplification of the initial reaction. Probably the eosinophils play a fundamental role ar this stage. The alveolar macrophages are equally implicated in this inflammatory reaction. Bronchial inflammation appears as a result of complex cellular reactions, regulated by chemical mediators. The most obvious consequence of bronchial inflammation is the delayed bronchial reaction. The experimental model contributes to physio-pathological understanding and a characterisation of the inflammatory components is observed principally in those patients with severe asthma. Agents capable of causing or aggravating bronchial hyper-reactivity can also induce bronchial inflammation. From this observation the idea is born of a relation between the concept of bronchial hyper-reactivity and bronchial inflammation. Acquired bronchial hyper-reactivity evolves in parallel to the symptoms and its intensity is correlated with the severity of the asthma. An understanding of the inflammatory mechanisms without doubt will bring new therapeutic perspectives.

Asthma↗

A comparative randomized double-blind clinical trial of hexapneumine and clistine as antitussive agents.

The efficacy and safety of a new antitussive expectorant drug hexapneumine was compared with that of an already marketed and functionally related clistine in a double-blind, randomized, parallel design clinical trial. A total of 100 patients with cough associated with chest diseases participated in the trial. Five patients (hexapneumine 3 and clistine 2) were lost to follow-up. Ninety-five patients (hexapneumine 46, clistine 49) completed the trial. Hexapneumine was significantly more effective (p less than 0.02) than clistine in suppressing cough as recorded from the patient's subjective improvement in the severity of the symptom. The side-effects observed were mild in nature and did not require reduction in dosage or withdrawal of the drug in any of the patients. Drowsiness and dryness of mouth were the predominant side-effects and were relatively more common in the clistine group as compared to hexapneumine. In the experimentally induced cough in 8 healthy human volunteers subjected to crossover design of study at weekly interval, hexapneumine and clistine were equally effective in suppressing cough. It is concluded that hexapneumine is a more effective antitussive as compared to clistine in naturally occurring cough. However, in experimentally induced cough the two drugs were equally effective. Hexapneumine exhibited relatively fewer side-effects.

Adolescent↗

Diagnosis of pneumonia: techniques and problems.

All diagnostic strategies in patients suspected of having pneumonia have considerable limitations. While the diagnostic strategy varies from patient to patient, an overview of one possible approach is summarized in Figures 2 and 3. The diagnosis and management of pneumonia usually poses little difficulty in the community setting, but the value of various diagnostic approaches in patients with hospital-acquired pneumonia is a subject of considerable controversy. Clinical criteria of pneumonia, including fever, purulent tracheobronchial secretions, leukocytosis, and a new infiltrate on chest radiograph are hampered by the high frequency with which these findings are observed in patients without pneumonia. Since tracheobronchial secretions are commonly contaminated by microorganisms colonizing the upper airways, routine culture of expectorated sputum, with the inevitable recovery of a potpourri of potential pathogens, can hardly be regarded as a meaningful exercise for the physician. Such cultures with subsequent extensive susceptibility testing form one of the largest workloads and expenses in microbiology laboratories. Clinical decisions based on such information may result in serious patient mismanagement with antibiotics, with the potential of superinfection and drug complication, which further add to hospital expenditures. Blood cultures are valuable when positive, but negative results are more common even in severe pneumonia. Transtracheal aspiration of tracheobronchial secretions is satisfactory in the diagnosis of community-acquired pneumonia in patients without pre-existing lung disease, but its value in the diagnosis of hospital-acquired pneumonia needs further evaluation. Transthoracic aspiration, especially with the newer finer needles, holds considerable promise but the significant risk of barotrauma deters most physicians from employing this procedure in patients requiring mechanical ventilation. Immunologic techniques of detecting microbial antigens, like countercurrentimmunoelectrophoresis and ELISA, are promising but presently inadequate to screen for a wide variety of organisms. Although it also has its limitations, fiberoptic bronchoscopy appears to be the most satisfactory technique if an invasive approach is being considered in a patient suspected of pneumonia. Samples taken with the plugged telescoping catheter technique, when properly performed, combined with quantitative cultures (and possibly antibody coating of bacteria) probably provide the least misleading information when a bacterial pathogen is being considered.(ABSTRACT TRUNCATED AT 400 WORDS)

Biopsy, Needle↗

The origins of secretions in the lower respiratory tract.

Normally the daily volume of lower respiratory tract secretions, in man, is probably less than 100 ml. In hypersecretory disease the volume increases sufficiently to cause cough and expectoration of secretions as sputum. The proportions which are sol or gel vary in disease as does the way in which constituent molecules partition in each phase. The constituent molecules and the cells which produce them (indicated in parentheses) may be classified as follows: 1. Mucus-glycoproteins present as droplets, or sheets (produced by mucous cells), periciliary fluid (serous or ciliated cell or a transudate), surface muco-substance (all epithelial cells) or surfactant hypophase (Clara or type II alveolar cells). 2. Proteins and peptides such as lysozyme (serous cell and macrophage), lactoferrin (serous cell and neutrophil), secretory piece (surface epithelium and submucosal glands), regulatory neuropeptides (dense-core granulated cell and both motor and sensory nerves) and fibronectin (alveolar macrophages). 3. Glycosaminoglycans such as heparan sulphate (epithelial membranes), heparin (mast cell), chondroitin sulphates and hyaluronate (connective tissue constituents). 4. Lipids including triglycerides (stored in cells) glycolipids (cell membrane), phospholipids (type II alveolar cells), sphingolipids (cell membrane), steroids (? Clara cells) and terpenes (cell membrane). 5. Anti-proteases and anti-oxidants such as bronchial protease inhibitors (serous anc Clara cells), alpha-2-macroglobulin (macrophage), alpha-1-antitrypsin (transudate) and anti-oxidants (type II alveolar cell and macrophage). 6. Other 'secretions' including ions and water (surface epithelium and submucosal glands), mediators of inflammation (migratory cell granules and their membranes), and serum proteins (present in transudate/exudate).

Animals↗

[Possibilities of active mass screening in the prevention of pulmonary hypertension in chronic bronchitis].

The authors presented a comparative analysis of the time course of pulmonary blood pressure (PBP), cardiac output, total pulmonary resistance (TPR), and right ventricular capacity in 2 groups of patients with chronic obstructive bronchitis (COB) with moderately marked emphysema and pneumofibrosis at repeated examinations with an interval of 4-36 (an average of 13) months. In the 1st group which was not actively followed-up, these indices showed a tendency to deterioration. In the 2nd group actively followed-up and receiving multimodality therapy (broncholytic drugs, expectorants, antibiotics when indicated, physiotherapy, in some cases--vasoactive agents and hormones) negative time course was much less frequent and noticeable. Positive PBP and TPR changes were twice as more frequent in the 2nd group. The efficacy of active medical examination of COB patients was shown with regard to the prophylaxis and therapy of pulmonary hypertension.

Adult↗

[Primary malignant mesenchymoma of the lung].

A case of a primary malignant mesenchymoma of the lung with elements of rhabdomyo-, leiomyo-, osteo-, fibro- and lipo-sarcoma is described. The tumor developed in a man of 58 with a long history of smoking, complaints of chest pains and cough with scanty sputum expectoration. The neoplastic process involved the upper lobe of the left lung and microscopically contained smooth muscle, endothelial, fibroblast-like cells, multinuclear giant cells resembling osteoclasts, strips of osteoid-like hyalinized connective tissue. Electron-microscopic examination revealed myoid-type cells with clusters of myofilaments and Z-type material, cells resembling fibroblasts, osteoclasts and lipocytes. It is suggested that there should be a common histogenesis of primary lung sarcomas arising from a stem cell precursor of mesenchymal origin in lung stroma, bronchial and vascular walls, pleura.

Humans↗

[Expiration of endogenous aerosol in chronic bronchitis and bronchial asthma patients].

The amount of expired endogenous aerosol in liquid drop and solid phases, 0.1-10.0 micron in diameter, in patients exceeded the normal indices. The nature of solid aerosol particle distribution by sizes was related to a degree of bronchial obstruction. The amount of both types of aerosols showed correlation with the amount of expectorated sputum.

Adolescent↗

Use of neostigmine to increase the rate of lung cancer detection by sputum cytology.

Neostigmine induction was investigated as a method for increasing the rate of detection of lung cancer in respiratory cytology samples. Eleven patients with dry and essentially nonproductive cough were given neostigmine, 15 mg by mouth or 0.5 mg by hypodermic injection. The quality of sputum produced was increased in all cases; the sputum was also more easily expectorated. Eight patients suspected of having lung cancer had previously negative cytologic examinations of sputum obtained by conventional methods. Following the administration of neostigmine, malignant cells indicating squamous-cell carcinoma were found in the sputum samples of three of these patients while dysplastic cells were detected in the samples from two patients. It is postulated that neostigmine intake may increase the excretion of mucous glands in the bronchial submucosa as well as the bronchial epithelium itself.

Carcinoma, Squamous Cell↗

[Pulmonary candida manifestation with cavitation in immunosuppressed patients].

The roentgenologic pattern of the pulmonary manifestation of candida species, resulting in a rapid development of pulmonary cavitations with mycetoma-like structures, was described in three patients. All patients, undergoing antineoplastic chemotherapy because of acute leukemia, presented with fever and expectoration, which were resistant to various antibiotic regimes. Cultures of blood and urine were sterile; but Torulopsis glabrata, a candida species, was found in multiple cultures of the sputum of all patients and also in a bronchoscopic lavage obtained from one patient after reconstitution of the granulopoesis. The roentgenologic appearance of the infiltrates was accompanied by a rise of the Ig-M immunoglobulins against candida. Following intravenous treatment with amphotericin B a reduction of the cavitation and of the infiltrates to small residues was observed. Simultaneously the body temperature and the sputum became normal and a fall in the immunoglobulin titers was found. The diagnostic problems of pulmonary cavitation and especially of pulmonary mycosis in immunosuppressed and therapy-induced granulocytopenic and thrombocytopenic patients with acute leukemia were discussed.

Acute Disease↗

[Use of miocamycin in the acute exacerbation of chronic obstructive bronchopneumopathy. Case material contribution].

18 patients with chronic obstructive bronchitis were treated with 900 mg myomycin a day. The clinical parameters examined were the quantity and organoleptic characteristics of the expectoration, coughing, and body temperature. These parameters were studied immediately before and 7.14 and 21 days after the start of treatment. Myomycin was found to be satisfactorily effective with minimal toxicity and well tolerated.

Aged↗

Ambroxol therapy in simple chronic bronchitis: effects on subjective symptoms and ventilatory function.

Ambroxol, a metabolite of bromhexine, was investigated in a double-blind, controlled trial using parallel groups. We studied the effects of 60 mg and 120 mg daily versus placebo in subjects with simple chronic bronchitis. Possible therapeutic effects were evaluated by means of interviews on subjective drug effects and current respiratory symptomatology, patient diary cards, and lung function tests. Ninety-seven subjects entered the study and 92 completed satisfactorily. Comparison with the placebo group at the end of the study showed that significantly more subjects in the 120 mg ambroxol group reported improvement in respiratory symptoms, principally improved expectoration. Subjects in the 120 mg group tended to prefer the treatment period when compared to placebo but the diary cards did not indicate significant changes. Lung function values were mainly normal and did not change during treatment. We conclude that the drug had a symptomatic effect and that further studies in more severely affected patients would be worthwhile.

Adult↗

[Antibiotic sensitivity of Pasteurella multocida and related bacteria (bacterial groups M5 and EF4). Studies of minimal inhibitory concentrations by agar dilution].

We have been isolating Pasteurella multocida and similar germs increasingly during the last few years: due to the rabies coming back in Eastern France, more consultations have been held following animal bites; samples are then taken for a bacteriologic research. We have studied their sensitivity towards 30 antibiotics. The determination of the MIC was achieved through the agar dilution method on 34 Pasteurella multocida of human origin issued after bites and expectorations, 4 EF4 and 4 M5. The Pasteurella are very sensitive to: beta-lactam antibiotics (the lowest MIC were observed for ureido-penicillins, amino-benzylpenicillins and third generation cephalosporins), chloramphenicol, cyclines and quinolones. Fosfomycin colistin and aminoglycosides are also active but with higher MIC. The macrolides have got a slow or no activity at all. The M5 are susceptible to the same antibiotics as Pasteurella but with slightly higher concentrations. Regarding EF4, minor sensitivity or resistance to penicillin G, cephalothin and cefamandole can be pointed out.

Anti-Bacterial Agents↗