Nonfibrous mineral particles in bronchoalveolar lavage fluid and lung parenchyma from the general population.

It is recognized that bronchoalveolar lavage (BAL) gives access to particulate matter present at the surface of the peripheral airspace. The objective of the present study was to evaluate the ability of BAL fluid analysis to predict the lung parenchymal particulate content. A BAL fluid sample, the parenchyma sample having undergone BAL, and an adjacent parenchyma sample that had not undergone BAL were obtained at autopsy on 10 individuals without any known recent occupational exposure to mineral particles. The particles (larger than 0.1 micron) were analyzed using a transmission electron microscope equipped with a microanalysis system. Nineteen types of particles were distinguished. The distribution of particle types in the three samples was compared. No significant difference between the relative concentrations was found, except for two particle types: fly ash (excess in BAL fluid compared with lavaged lung) and kaolinite (excess in lavaged lung compared with adjacent area). Such differences may be due to limitations in methodology. Although no correlation could be found between the absolute concentrations of particles in BAL fluid and in lung tissue, analysis of particles in BAL fluid may provide information on the types of particles present in the lung parenchyma.     

Mineral particles in the human bronchial mucosa and lung parenchyma. II. Cigarette smokers without emphysema.

The effects of cigarette smoke on the microanatomic deposition and retention pattern of exogenous mineral particles is unknown. To determine how cigarette smoke affects long-term particle retention in those with minimal smoke-related disease, we selected autopsy lungs from ten smokers without evidence of emphysema at autopsy, and used analytical electron microscopy to examine exogenous mineral particle concentration in the mucosa of seven different bronchi of varying sizes and four parenchymal sites fed by those bronchi. These data were compared with values from twelve lifetime nonsmokers. Overall, total mean particle burden in the parenchyma in the smokers and nonsmokers was similar, but there was a markedly decreased particle load retained in the smokers' airways. The consistent increase in particle burden seen in nonsmokers as airways became narrower and more distant from the carina was lost in many, but not all, of the smokers, especially for particles larger than 1 micron, and this effect did not appear to depend on amount of smoking. Rare polonium particles were found but were too sparse to use as a smoke distribution marker. However, calcium-containing particles, previously suggested by us to represent calcium carbonate actually derived from the smoke, were present in greatest concentration in the larger airways and distal parenchyma. These observations indicate the following in smokers without parenchymal smoke-induced structural damage: (1) Overall, cigarette smoking disrupts the normal retention (? deposition) pattern of particles in the airways. (2) Cigarette smoking leads to markedly decreased long-term retention of exogenous mineral particles in the airways without significantly affecting overall tissue particle retention. (3) The distribution of calcium particles in the airways and parenchyma in smokers is similar to that predicted in a recently published model of smoke particle deposition, and further supports the idea that calcium-containing particles can be used as a direct tracer of smoke particle deposition. In the present study this distribution indicates that the large airways and parenchyma receive the greatest smoke deposition. (4) Within the group of smokers, some people appear resistant to the disruptive effects of smoke on particle retention patterns, whereas other people smoking comparable amounts show markedly abnormal retention patterns. The latter may have unusual sensitivity to cigarette smoke and perhaps susceptibility to smoke-induced diseases.     

Chronic eosinophilic pneumonia with small abscesses in the tracheo-bronchial mucosa and lung parenchyma.

Abscess formation is uncommon in eosinophilic lung disease. In this paper we present a case of chronic eosinophilic pneumonia in which bronchofiberoscopy revealed scattered small abscesses in the large airways. Pathological examination revealed the presence of inflammatory cells with eosinophilic infiltration in both the bronchial mucosa and lung parenchyma.     

Aminopeptidases and angiotensin I-converting enzyme activities in primary human lung tumors and lung parenchyma.

The activities of alanyl aminopeptidase (AAP), arginyl aminopeptidase (RAP), alpha-glutamyl aminopeptidase (EAP) and angiotensin I-converting enzyme (ACE) were investigated in primary human lung tumors of different histological types and in matched lung parenchyma. In contrast to the studied aminopeptidases whose activity differences between tumor and lung tissues were infrequently significant, the activity of ACE was decreased highly significantly in the majority of lung tumors.     

Distribution of bronchial nonspecific reactivity in the general population

We investigated 654 subjects of a small Lombardy (Italy) town between 15 and 64 years of age who were representative of the general population. By clinical examination, the sample included 535 normal subjects (164 normal smokers, 341 normal nonsmokers, 30 normal subjects with acute upper respiratory illness within 30 days before the challenge), 50 with chronic bronchitis, 26 with asthma, and 43 with allergic rhinitis. Subjects whose FEV1 was 75 percent or more than the predicted value (654) underwent methacholine bronchial challenge by means of 1 percent metered-dose solution. The test result was considered positive at a drop of more than 15 percent in FEV1 (compared with buffer). Normal smokers and all of the groups with disease had a significantly different distribution of reactivity compared with normal nonsmokers. The difference between asthmatic and these "normal" subjects was highly significant; nevertheless, a clear cut-off between the two groups does not appear to exist.     

L-carnitine does not exert any in vitro relaxant effect in Guinea pig trachea,lung parenchyma and human bronchial tissue

The aim of the present study was to investigate the probable in vitro relaxant effect of carnitine in guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissue. It was suggested by an in vivo study that carnitine pretreatment prevented the subclinic bronchospasm in children who underwent chronic hemodialysis. Tracheal and lung parenchymal preparations of 10 guinea pigs and 5 human bronchial tissues were prepared and mounted in 20-mL organ baths. In the first series of experiments, contractions to carbachol and histamine (10(-9) to 10(-3) M) were compared after the tissues were incubated with different concentrations of L-carnitine (10(-6) to 10(-4) M). pD(2) values were compared with analysis of variance (ANOVA) and P <.05 was considered as significant. In the second part of experiments, the inhibitory effect of L-carnitine (10(-9) to 10(-3) M) was investigated on the sustained contractions of preparations to carbachol (10(-6) M) and histamine (10(-5) M). In the first part of the study pD(2) values obtained with carbachol were 6.48 +/- 0.09, 5.42 +/- 0.05, and 6.48 +/- 0.02 for guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissues, respectively. pD(2) values obtained with histamine were 5.34 +/- 0.10, 5.74 +/- 0.06, and 6.32 +/- 0.03 for guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissues, respectively. No significant difference was observed between the pD(2) values before and after incubation with carnitine (P >.05). In the second part of the study, only 10(-4) M L-carnitine exerted an insignificant relaxant effect (6.16% +/- 1.22% on carbachol induced contractions and 4.48% +/- 0.85% on histamine induced contractions) in guinea pig trachea. Our results show that L-carnitine exerts no in vitro relaxant effect in guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial preparations.     

Glomus tumor in the lung parenchyma

Glomus tumors are uncommon lesions of glomus cell origin with ultrastructural and immunohistochemical features of smooth muscle. In the majority of the cases reported in the literature glomus tumors are benign, but there are some rare cases in which they demonstrate aggressive and malignant clinical and histological features. Glomangiosarcomas of the lung are extremely rare malignant tumors, because of the fact that glomus bodies are rare or absent. Due to their rarity they are misdiagnosed. Surgical resection is considered to be the most effective treatment for this condition. We report a case of a 35 year old female with a pulmonary glomangiosarcoma.KEY WORDS : Glomangiosarcoma, misdiagnosis, surgical resection     

Irritable bowel syndrome, gastro-oesophageal reflux, and bronchial hyper-responsiveness in the general population

Background—Associations have been shown betweenirritable bowel syndrome (IBS) and gastro-oesophageal reflux, betweengastro-oesophageal reflux and asthma, and more recently between IBS andbronchial hyper-responsiveness (BHR).
Aims—To explore the inter-relations between these conditions.
Subjects—A randomly selected community sample of4432adults.
Methods—A validated postal symptom questionnaireinvestigating the associations between IBS, gastro-oesophageal refluxsymptoms, and symptomatic BHR.
Results—3169 questionnaires (71.7%response) returned by 1451 men and 1718 women were analysed. One yearprevalences, in men and women respectively, of IBS were 10.5% and22.9%, of dyspepsia 26.3% and 25.25%, of gastro-oesophageal refluxsymptoms 29.4% and 28.2%, of BHR 13.2% and 14.6%, and of chronicbronchitis 8.3% and 4.9%. Logistic regression showed independentassociations between IBS and BHR, gastro-oesophageal reflux symptoms,and dyspepsia. There was no significant independent association betweenIBS and chronic bronchitis. In men and women the odds ratio with 95%confidence interval (CI) for IBS and gastro-oesophageal reflux symptomswas 2.6 (2.1-3.1; p<0.001) and for IBS and BHR 2.1 (1.7-2.7;p<0.001). These associations held on stratifying for sex andconsultation behaviour. IBS, gastro-oesophageal reflux symptoms, andbronchial hyper-responsiveness occurred more frequently together thanexpected, 2.5% (95% CI 2.41-2.57) of the sample having all threeconditions compared with an expected prevalence of 0.7% (95% CI0.66-0.71). The conditions were independently associated with each other.
Conclusions—These observations may indicate thepresence of an underlying disorder producing symptoms ingastrointestinal and respiratory systems.

     

Immunological studies on bronchial secretion. I. Antigenic relationship between bronchial secretion and serum: bronchial secretion constituents detected in human sera.

Rabbit anti-human bronchial secretion serum yielded, by double gel-diffusion, 5 precipitation bands with the homologous antigen. This anti-bronchial secretion serum reacting with 150 human sera (86 from patients with asthma, 17 from patients with tuberculosis, 25 from patients with other diseases and 22 normal sera) showed 1 to 3 precipitation bands in 136 sera, 4 precipitation bands in 13 sera and 5 precipitation lines in 1 serum. Precipitation bands with identity reactions were obtained when the anti-sputum sera reacted simultaneously with human sera and bronchial secretion. Identity reactions were also obtained when the anti-bronchial secretion serum absorbed with normal human sera reacted with bronchial secretion and human sera from six patients and one normal individual. The number of precipitation bands in some sera was not the same after 1 or 2 years. Based on these immunological data, the physiological concept of expectoration, according to which part of the bronchial secretion may be absorbed, was discussed.     

An elastase-specific inhibitor from human bronchial mucus. Pathogenesis in lung emphysema

Under physiological conditions human bronchial mucus contains an elastase-specific inhibitor which is quite different from hitherto known inhibitors: alpha 1-antitrypsin, HI-30, and BSI-TE. In bronchial mucus of 100 patients suffering from obstructive airway disease the amount of this inhibitor specific against elastase from both pancreas and polymorphonuclear neutrophilic leucocytes was measured. A group of 18 patients showed no inhibitor in their native mucus rather than free elastolytic activity. Another group of 82 patients had no elastolytic activity in their native mucus but free anti-elastolytic activity together with varying amounts of elastase-specific inhibitor bound to proteases. In a total of 20 cases from both groups the inhibitor was not detectable, neither in a free nor in a complexed form. Presuming that there is no hereditary deficiency involved, a strong importance of inactivating reactions such as oxidation is concluded.     

Immunologic "memory" for microbial antigens in lymphocytes obtained from human bronchial mucosa.

Memory for previous immunologic contact with microbial antigens has been detected in lymphocytes from human bronchi as a secondary immune response, when tested in vitro. Antigens stimulated a predominantly proliferative response in blood lymphocytes that was significantly greater than the response in mucosal lymphocytes with purified protein derivative and Herpes simplex type 1 antigens. Co-culture experiments with autologous blood lymphocytes showed that cell-dependent suppression was one mechanism of the low response of bronchial lymphocytes. In the patient who inhaled a foreign body, a proliferative response to antigens was restricted to bronchus-associated lymphoid tissue lymphocytes, suggesting a recruitment of antigen-reactive cells from a circulating pool.     

Deposition of large particles in human lung

Twenty-four nonsmoking males, all without history of pulmonary disease, were randomly divided into four groups of six subjects each. The subjects in each group inhaled monodisperse Teflon particles labelled with 111In (half-life 2.83 days); 8.2, 11.5, 13.7 and 16.4 micron aerodynamic diameter, respectively. Radioactivity in head and throat, lung and stomach was determined after 0, 3 and 24 hrs using a profile scanner. For some subjects radioactivity was also determined using a whole-body scanner at 3.5 and 24 hrs. After the 24-hr determination the subjects inhaled labelled Teflon particles again, this time with a filter in front of the mouth. Average values for total deposition in the body, obtained using a profile scanner, whole-body scanner and filter measurements, agreed fairly well. Lung retention values obtained by whole-body and profile scanning also agreed well. The average deposition in the lung, expressed as a percentage of total deposition, was 49, 31, 21 and 13% for the four particle sizes (8.2-16.4 micron). Alveolar deposition, determined as retention at 24 hrs and expressed in percent of total deposition, was 15, 4, 4 and 1%. For the smallest particle sizes the deposition values agreed with earlier investigations. However, for the larger particles the two deposition values were higher than expected when compared to earlier studies.     

Genetic and biochemical markers of obstructive lung disease in the general population

Introduction: New markers of early disease activity and prognosis are needed in asthma and chronic obstructive pulmonary disease (COPD). Objective: To identify new markers of asthma and COPD to implement in clinical practice, we genotyped for common genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), α₁‐antitrypsin, and mannose‐binding lectin (MBL) genes, and measured baseline fibrinogen and C‐reactive protein (CRP) concentrations in up to 9245 adults randomly selected from the Danish general population. Materials and Methods: Information on diagnoses of asthma and COPD was collected from two Danish National Registers covering all hospital discharges and deaths in the country. This data was correlated with genotyping results to determine risk of obstructive lung disease according to the genetic and biochemical markers studied. Results: The genetic marker, F508del, in the cystic fibrosis gene was associated with increased asthma risk, but aggregating this data in a meta‐analysis with results from previous reports, the risk of asthma was only marginally elevated [summary odds ratio (95%CI): 1.3 (1.1–1.6)]. The F508del marker was not associated with COPD [odds ratio: 0.9 (0.4–1.6)]. Our data also suggested a significant role of smoking on fertility in cystic fibrosis/F508del heterozygotes. The risk of COPD was marginally elevated for the genetic markers, MS and MZ, in the α₁‐antitrypsin gene [summary odds ratio: MS, 1.2 (1.0–1.4) and MZ, 2.3 (1.6–3.4)], whereas the SZ marker was an important risk factor of COPD [summary odds ratio: 3.3 (1.2–8.6)]. The ZZ genotype is already in clinical use as a genetic marker for early‐onset COPD. Our data also suggested ZZ and MZ are associated with reduced blood pressure and MZ with reduced risk of ischemic cardiovascular disease. Genetic deficiency of MBL was not a major risk factor for asthma [relative risk: 1.1 (0.8–1.7)] or COPD [1.4 (0.97–2.0)]. We found increased risk of cardiovascular disease with MBL deficiency, but this result could not be confirmed in a matched case‐control study using cases with ischemic cardiovascular disease from Copenhagen University Hospital, Denmark. Elevated serum fibrinogen and CRP levels were biochemical markers of future COPD. In the future after further validation, it is possible that these markers, particularly CRP, can be used to categorize individuals with low, medium, or high risk of COPD, and thus point out patients in need of intensified prevention and treatment for COPD. The association between COPD and elevated fibrinogen and CRP levels suggests that either factor or upstream factors regulating fibrinogen and CRP expression are important players in the pathogenesis of COPD. Conclusion: We have set‐up an analysis for diagnosing the SZ and ZZ genotypes at the Department of Clinical Biochemistry at Herlev University Hospital, together with measurement of plasma α₁‐antitrypsin levels. This will help clinicians to detect α₁‐antitrypsin‐deficient individuals with a high risk for COPD, and opens up for early smoking prevention counseling and potential therapy for individuals identified with α₁‐antitrypsin deficiency. The F508del marker and genetic variants in the MBL‐2 gene cannot at present be used as markers for obstructive lung disease in the Danish general population. To determine whether fibrinogen or CRP is causally related to COPD, we are currently investigating whether genetically reduced levels of fibrinogen and CRP are associated with reduced risk of future COPD. The studies were supported financially by the Danish Medical Research Council, the Danish Lung Association, and the Danish Heart Foundation.     

Airway narrowing in porcine bronchi with and without lung parenchyma.

During bronchoconstriction elastic after-loads arise due to distortion of lung parenchyma by the narrowing airway. In the present study, the functional effect of parenchymal elastic after-load on airway narrowing was determined. Airway narrowing was measured in vivo over a range of transpulmonary pressures and compared with in vitro narrowing measured at corresponding transmural pressures. Bronchi were generation 10 with internal diameters of approximately 4 mm. In vivo luminal narrowing was measured by videobronchoscopy in anaesthetised and ventilated pigs. In vitro luminal narrowing was measured by videoendoscopy in isolated bronchial segments. Airways were activated by maximum vagal nerve stimulation and maximum electrical field stimulation in vivo and in vitro, respectively. At 5 cmH2O, stimulation produced a 35.9+/-3.2% (n = 6) and a 36.5+/-2.4% (n = 11) decrease in lumen diameter in vivo and in vitro, respectively. At 30 cmH2O, luminal narrowing fell to 23.7+/-2.0% in vivo and 23.4+/-2.5% in vitro. There was no difference between luminal narrowing in vivo and in vitro at any pressure. In conclusion, these findings suggest that in mid-sized, cartilaginous bronchi, parenchymal elastic after-loads do not restrict airway narrowing.