Marked Airway Research Articles

Myosin Isoform Expression in Developing and Remodeling Rat Lung

The tissue distribution of myosin isoforms was examined in developing smooth muscle of rat lung. Antisera employed included a general smooth muscle myosin antibody (aSMMG) and two smooth muscle myosin isoform specific antisera (aSM1 and aSM2). In the pseudoglandular, canalicular, and saccular lung, the isoform-specific aSM1 antiserum was very lightly reactive only with large airway and not reactive with vascular smooth muscle, whereas aSM2 was unreactive with any lung cells. During these same stages, the aSMMG serum reacted well with the mesenchymal coat around the larger airways, declining in intensity as the tube size diminished. Vascular smooth muscle elements had only moderate reactivity at this time. In the adult, aSM1 marked airway smooth muscle as well as the tips of the alveolar septae. Vascular reactivity was seen in both arterial and venous elements. An identical distribution of reactivity was seen for aSMMG. aSM2 reactivity appeared confined primarily to airway smooth muscle and was absent from all but the largest vascular structures. Companion Western blot analyses confirmed the presence of SM1 in fetal and mature tissues as well as the relative lack of SM2 in all but the fully differentiated airways. Lung injury due to intratracheal instillation of bleomycin is characterized by a proliferation of mesenchymal cells similar to immature smooth muscle cells. These cells express smooth muscle forms of actin but lacked the mature smooth muscle myosin isoforms. In summary, differentiation of smooth muscle in the lung proceeds with progressive replacement of nonmuscle isoforms of myosin with differentiation-specific forms. In this regard, the maturation of vascular muscle tissue lags behind that of nonvascular (visceral) muscle structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Viruses as precipitants of asthma symptoms. II. Physiology and mechanisms.

The upper and lower airways have complimentary roles in the ultimate object of supplying the body with oxygen whilst removing waste products of metabolism. Pathology in one area may trigger a response in another, the physiology of which, in the case of virus-induced asthma exacerbations remains poorly characterized. Viral infection of the upper airways by common cold viruses frequently triggers a response in the lower airways leading to prolonged morbidity, especially in subjects with significant pre-existing airway disease. The induction or amplification of BHR may be an important mechanism whereby asthmatic symptoms are produced although the cellular and tissue events or reflex mechanisms activated by viral illnesses and underlying BHR changes are poorly defined and may be dependent on the type and the severity of infection. Children and asthmatics tend to develop frequent colds setting in motion a sequence of events culminating in airway obstruction and symptoms of wheezing, coughing and chest tightness. This may reflect independent inflammatory changes caused by a simply additive effect of viral damage to the mucosa superimposed upon pre-existing allergic inflammation (Fig. 1). Few if any symptoms will develop in normal subjects with a mild cold whereas significant symptoms may ensue if the cold is severe and induces marked lower airway swelling, secretions and smooth muscle contraction; pathology to which children who have small calibre airways may be particularly susceptible. In asthmatics even a mild cold frequently induces exacerbation of symptoms, while serious life-threatening asthma attacks may occur associated with a severe cold. Some studies have suggested that this effect is not only additive but also synergistic and brought about by release of the mediators already present in increased quantities, the induction of IgE synthesis, or by the potentiation of neural and epithelial damage. The combined effect of both asthma and viruses may thus be amplified and result in a sustained and refractory period of airway obstruction, severe symptoms and unstable asthma. As most hospital admissions for asthma occur over the winter months and soon after the start of the school terms [115], spread of viruses through the community to susceptible individuals may be the single most important cause of sustained exacerbations of asthma. Definition of the pathological and physiological mechanisms involved will lead to better understanding and may thus provide a basis for prevention and the development of effective forms of treatment for virus-induced asthma.

Effects of single and multiple inhalations of antigen on airway responsiveness in monkeys

Airway hyperresponsiveness is an important and characteristic feature of asthma. In monkeys, we have reported that antigen (Ag) inhalation induces a prolonged airway eosinophilia, that chronic airway eosinophilia is associated with marked airway hyperresponsiveness, and that chronic Ag inhalations induce airway eosinophilia and hyperresponsiveness. In this study we have determined the effects of acute Ag inhalation(s) on airway responsiveness to obtain a protocol for the study of the mechanisms involved. Anesthetized and intubated adult male cynomolgus monkeys with a naturally occurring sensitivity to Ascaris suum extract were studied. Airway responsiveness (provocative concentration of nebulized and inhaled methacholine that induced a 100% increase in respiratory system resistance [Rrs] [PC 100]; twofold decrease regarded as significant) and airway cell composition (bronchoalveolar lavage [BAL]) were determined 1 day before and 20 hours after a single inhalation of Ascaris extract, or 3 days before and 3 days after three alternate-day inhalations of Ascaris extract. The single inhalation of Ag (N = 7) caused an acute increase in Rrs (307% ± 62%), an increase in BAL leukocytes, and a decrease in PC 100 in three animals that was moderate (more than eightfold) in two animals. The mean ± SE change in log PC 100 was only −0.25 ± 0.24. The multiple inhalations of Ag in the same animals caused acute increases in Rrs (178% ± 48%, 380% ± 83%, and 331% ± 63%, respectively), an increase in BAL granulocytes, and a decrease in PC 100 in six of seven animals (mean ± SE change in log PC 100 was −1.36 ± 0.34) that was moderate in two and severe (more than 80-fold) in three animals. In summary, multiple (but not single) inhalations of Ag induce an increase (usually more than eightfold) in airway responsiveness in most monkeys.

Different Patterns of Pulmonary Sequelae after Hyaline Membrane Disease: Heterogeneity of Bronchopulmonary Dysplasia?

In an autopsy study of 37 infants who suffered from hyaline membrane disease (HMD), two distinct patterns of pulmonary lesions could be defined. One pattern, characterized by marked interstitial fibrosis in the absence of airway abnormalities, was labelled 'interstitial-type' histology. A second type, labelled 'bronchiolar-type' histology, showed marked airway lesions and alveolar emphysema. Nine patients of each type were analysed. Nineteen other patients had a 'mixed-type' histology and were not further studied. Retrospectively, the clinical and radiological characteristics of both series were analysed. No differences in birth weight, gestational age and initial radiological HMD grade could be demonstrated. The pulmonary function of the bronchiolar-type patients however was significantly worse at the onset, and these infants needed more oxygen and ventilatory support during the first 10 days of life. They all died from respiratory failure whereas 4 patients from the interstitial group had non-pulmonary fatalities. In the bronchiolar group chest X-rays showed atelectasis and pulmonary interstitial emphysema in the early stages, and hyperinflation with bullae and irregular streaky densities in the later. Patients in the interstitial group had no or minor emphysema with more homogeneously spread densities over both lungs. We conclude that both types of evolution represent two extremes of the bronchopulmonary dysplasia spectrum.

Inflammatory Markers in Bronchoalveolar Lavage and in Bronchial Biopsy in Asthma during Remission

Bronchoalveolar lavage and BB were performed in 13 asthmatic and six healthy subjects to characterize cellular markers of inflammation in BAL and BB; to compare cellular profile of BAL with cell infiltration in BB; to examine the relationship between bronchial responsiveness and markers of inflammation in BAL and BB. Eosinophils and mast cells were increased in BAL in asthmatic subjects; eosinophils were positively correlated with neutrophils and mast cells. Epithelial shedding was present in nine asthmatic and five control subjects. Intraepithelial cells and cells in submucosa were increased in asthmatic subjects. Eosinophils and intraepithelial mast cells were higher. Thickened basement membrane was associated with more marked cell infiltration in submucosa. Ciliated cells in BAL relate to intraepithelial cells; cells in BAL broadly reflect cell infiltration of submucosa. In the asthmatic group, the degree of bronchial responsiveness correlated with ciliated cells in BAL and with intra-epithelial cells in BB. Marked airway inflammation is associated with stable asthma; inflammatory changes within bronchial epithelium may be linked to the development of bronchial hyperresponsiveness.

Transcarinal Aspiration of a Mediastinal Cyst to Facilitate Anesthetic Management

Marked airway obstruction and interference with gas exchange was encountered following institution of general anesthesia for resection of a cystic subcarinal mass. Intraoperative bronchoscopy revealed marked airway compression. The cyst was decompressed using a transbronchial needle through a fiberbronchoscope. This allowed for safe anesthetic management and resection of the mass.

Neuroblastoma of the thoracic inlet

The case of a 5-month-old girl with a large neuroblastoma of the thoracic inlet, an unusual location for this tumor, is presented. The patient had marked airway compromise due to tumor compression, with extension of the mass through the thoracic inlet into the base of the neck, also incorporating the right subclavian artery. The highly unusual location of this tumor is presented, and challenging technical aspects of its management are discussed.

Oxygen radicals in capsaicin-induced bronchoconstriction

The role of oxygen radicals in capsaicin-induced bronchoconstriction was investigated using scavengers of the radicals. A total of 48 guinea pigs weighing 293 +/- 7 g were employed in this study, which consisted of two phases. In phase 1, 35 anesthetized paralyzed animals were divided into five groups: group 1A, control (n = 6); group 1B, chronic dimethylthiourea (DMTU, n = 12); group 1C, acute DMTU (n = 6); group 1D, superoxide dismutase (n = 4); and group 1E, catalase (n = 7). All animals were injected with capsaicin (16 micrograms/kg iv), and changes in respiratory compliance and maximal expiratory flow rate were used as indicators of bronchoconstriction. The capsaicin injection caused a marked airway spasm that was significantly ameliorated by chronic DMTU pretreatment, but no amelioration was noted with the other treatments. An additional study for group 1C was performed using a double dose of DMTU. Again no amelioration was found. In phase 2, 13 animals were divided into two groups: group 2A, substance P (SP, n = 7) and group 2B, chronic DMTU + SP (n = 6). There was no significant difference in SP-induced bronchoconstriction between animals in these two groups. These data suggest that capsaicin-induced airway constriction is modulated by oxygen radicals which may augment mainly on the biosynthesis and/or axonal transport of tachykinins.

Pathological and haematological responses of cats experimentally infected with Toxocara canis larvae

Responses of eight adult cats to one or two infections with larvae of Toxocara canis were studied up to 39 days post infection (DPI). Clinically, all cats remained normal throughout the study. The major necropsy finding was multifocal, white to grey nodules mainly within the liver, lungs and kidneys; live larvae were found in liver nodules, Histologically, the nodules were eosinophilic granulomas. Granulomas containing a larval section were observed mainly within the liver. All infected eats had variably severe, eosinophilic arteritis and bronchiolitis and medial hypertrophy and hyperplasia of the pulmonary arteries. No inflammatory eye lesions were detected. Circulating eosinophil levels increased in all infected cats; peak values of 15,790 and 10,050 eosinophils μ −1 were observed at 25 or 32 DPI in cats receiving a single or double infection, respectively. Bone marrow of all infected cats exhibited marked eosinophilic hyperplasia which did not correlate with the level of circulating eosinophilia. Thus, infection of cats by the larvae of T. canis causes disseminated eosinophilic and granulomatous disease with marked pulmonary artery and airway lesions.

土砂による気道閉塞症例

The patient was a ten-year-old boy who was buried under pebbly soil and suffered from marked airway obstruction.He was transferred from a docter by an ambulance with oxygen inhalation. On arrival, he was nearly apneic and unconscious. Arterial blood gas analysis revealed pH 6.581, PaO2 400.2Torr, PaCO2 162.0Torr. Tracheotomy was done and most foreign bodies had been removed under bronchoscopy and by airway washing. Nine hours after removal, his consciousness was recovered. The pebbles in the right subsegmental bronchus B8b were removed using bronchofiberscope later on. The tracheal stoma was obliterated four days later. He was discharged from the hospital after fifteen days' stay without any complications, e. g., pneumonia, emphysema, tetanus nor sequelae.Foreign bodies, in this case, were mixture of soil and pebbles of various sizes, and were removed effectively by different maneuver, i. e., soil by airway washing, pebbles in bronchi by bronchoscopy and pebbles in peripheral bronchus by bronchofiberscopy. Needle insertion into the airway through cricothyroid membrane seemed to be of crucial efficacy for the initial respiratory resuscitation.

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

Toluene diisocyanate-induced airway hyperreactivity and pathology in the guinea pig

We assessed the nature and progression of airway mucosal disease and histaminic reactivity in English short-haired guinea pigs at 2, 24, 72, 168, and 504 hours after toluene diisocyanate (TDI) exposure (4 hours of 3 ppm of TDI for 5 consecutive days). To also determine whether TDI-specific, IgE-like antibodies developed in TDI-exposed animals, passive cutaneous anaphylaxis testing was done 28 days after TDI. Bronchial reactivity was determined serially by measuring specific airway conductance as a function of increasing doses of aerosolized histamine in six exposed and three control animals studied intact and unanesthetized. The remaining 10 exposed and 10 control guinea pigs were sacrificed in groups of two at each time point to obtain airway tissue for light microscopic examination. We found that airway hyperreactivity to histamine occurred after TDI in all animals tested. It was maximal 2 hours after the 5-day exposure and remitted by 72 hours. In addition, marked airway obstruction occurred after TDI that persisted for at least 168 hours. There were dramatic signs of airway mucosal damage associated with the bronchial hyperreactivity that included substantial decreases in epithelial cilia, mucin content, and mast cells, as well as squamous metaplasia, numerous mitotic figures, and a prominent polymorphonuclear leukocytic infiltrate. Passive cutaneous anaphylaxis tests in exposed animals were negative. Our results suggest that TDI-induced bronchial hyperreactivity may be related to airway mucosal injury and inflammation.

Pathophysiology and Management of Severe Asthma

Severe asthma is characterized by marked airway obstruction caused by mucus plugging, airway edema and inflammation, and contractions of airway smooth muscle. This leads to a complex series of pathophysiologic events that can be reversed with vigorous treatment given for a sufficient period of time. Standard treatment includes not only bronchodilating agents and corticosteroids but in some instances mechanical ventilation.

Management of laryngo/tracheal stenosis— Reconstruction with epiglottic mucoperichondrial flap

More emphasis should be given to the prevention of laryngotracheal stenosis. Blunt or crushing injuries to the larynx must be immediately and accurately evaluated. Marked airway obstruction, exposed cartilage in the laryngeal lumen, significant subcutaneous emphysema or fracture of the cricoid cartilage necessitates an open exploration as promptly as practicable. Primary closure of the mucosal tears, reposition of displaced fractured cartilages and internal splinting and proper positioning of the tracheostomy will prevent the occurrence of laryngeal stenosis. In case the stenosis has occurred, we feel reconstruction by epiglottic mucoperichondrial flap with hyoid sternohyoid pedicle graft will give good results. This procedure is one more step towards the goal of success in treating the laryngotracheal stenosis though the final answer is yet to be told.

Bronchiolitis in Rheumatoid Arthritis

Bronchiolitis in association with rheumatoid arthritis has been reported, to our knowledge, in 18 patients to date. In some cases use of penicillamine has been strongly associated with the development of bronchiolitis. Most of the reported cases are described as having marked irreversible airways obstruction and hyperinflation. We describe a patient with rheumatoid arthritis whose respiratory tract symptoms began during gold therapy. Physiologic studies showed marked lung hyperinflation without pathologic findings in forced dry spirometric study. On open lung biopsy a mild degree of granulomatous bronchiolitis was found. Immunofluorescent microscopy showed IgM- and IgG-containing plasma cells in the bronchiolar walls.

The number and distribution of mast cells in monkey lungs.

We estimated the number of mast cells in monkey lungs by both quantitative histologic examination and measurement of total lung histamine, and showed that monkey lungs contain between 10(7) and 10(8) mast cells, with approximately 83% of these being located in conducting airways, and 17% in the parenchyma. The number of mast cells found in each airway generation increased from approximately 60,000 in the trachea to 8 million in the terminal bronchioles. In airways from different generations the number of mast cells superficial to the basement membrane in the epithelium and lumen (EMC) was compared to the number of mast cells found in the submucosa between basement membrane and cartilage and to the number of those found outside the cartilage. The number of EMC varied between animals and ranged from 0-0.4% of the total number of mast cells in the trachea, to 0-27% of the total in the terminal bronchioles. On the average, EMC accounted for 12% of the total number of mast cells in conducting airways, where we calculate that there is approximately one EMC for every 100,000 epithelial cells. Eosinophils were distributed in close relation to mast cells in the mucosa and submucosa, but were rare outside the cartilage. We conclude that the number of mast cells increases from central to peripheral airways and that this may account for the marked peripheral airway response observed after antigen challenge.

PERCEPTION OF ASTHMA

Subjective assessment and objective measurements of airways obstruction were compared in 82 patients during methacholine-induced asthma. 15% of the patients were unable to sense the presence of marked airways obstruction (forced expired volume in 1 s less than 50% of the predicted normal value). These subjects could not be characterised as a distinct group on the basis of their sex, age, or duration of their asthma. This reinforces the need for objective measurement of lung function in the management of asthma.

Pulmonary function in bronchial carcinoma.

Legge, J. S., and Palmer, K. N. V. (1973). Thorax , 28 , 588-591. Pulmonary function in bronchial carcinoma. Pulmonary function was measured preoperatively in 330 patients with bronchial carcinoma. Obstructive bronchitis was present in 62%. Of 225 patients considered fit for thoracotomy and lung resection, 13 developed postoperative ventilatory failure and six died of this. Those who developed ventilatory failure had more marked airway obstruction, lung hyperinflation, and higher arterial carbon dioxide tensions, and also increased respiratory frequencies and physiological dead space/tidal volume ratios on exercise.

Bronchiectasis following Heroin Overdose: A Report of Two Cases

Two patients developed respiratory insufficiency following episodes of heroin overdose complicated by aspiration. In both instances pulmonary function testing demonstrated marked obstructive airway disease and arterial hypoxemia. Bronchograms performed on both of these patients demonstrated bronchiectasis. The persistence of respiratory insufficiency into the recovery phase of heroin pulmonary edema may indicate the onset of chronic pulmonary disease. Pathology of the bronchial tree should be looked for in evaluating this syndrome. Two patients developed respiratory insufficiency following episodes of heroin overdose complicated by aspiration. In both instances pulmonary function testing demonstrated marked obstructive airway disease and arterial hypoxemia. Bronchograms performed on both of these patients demonstrated bronchiectasis. The persistence of respiratory insufficiency into the recovery phase of heroin pulmonary edema may indicate the onset of chronic pulmonary disease. Pathology of the bronchial tree should be looked for in evaluating this syndrome.

Patterns of distribution and clearance of aerosols in patients with bronchiectasis.

Pulmonary distribution and clearance of inhaled aerosols were studied in 14 patients with bronchiectasis confirmed by bronchography. Abnormalities in the deposition of the particles were present in 8 patients, who demonstrated a central deposition of particles in the lungs; such a pattern of deposition is abnormal for the size of particles and the pattern of breathing used during inhalation. These 8 patients had more marked airway obstruction and more severe symptoms of chronic bronchitis. Fewer particles were deposited in areas with localized saccular bronchiectasis than in the contralateral nonbronchiectatic areas. Abnormalities in clearance were apparent in all patients. They were characterized by abnormally slow clearance rates immediately after inhalation of the particles and by the presence in the photoscintigrams of juxtahilar areas of accumulation of particles. There were no significant differences between these patterns of clearance and those found in patients with bronchitis without bronchiectasis.