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PubMed2005

[National cohort of patients with emphysema and alpha-1 antitrypsin deficiency].

BACKGROUND: The natural history and optimal therapeutic management of emphysema associated with alpha-1 antitrypsin deficiency are poorly understood. The purpose of this cohort of patients with emphysema associated with alpha-1 antitrypsin deficiency is to describe their characteristics and to study the factors associated with the evolution of their pathology. MATERIALS AND METHODS: It is a multicentre, prospective, cohort study including all the patients in metropolitan France with alpha-1 antitrypsin deficiency associated with emphysema (diagnosed by CT scanning) and an obstructive ventilatory defect. All respiratory physicians will be approached. Patients meeting the inclusion criteria will be followed up every 6 months for 5 years. Clinical and spirometric data as well as those relating to quality of life will becollected. The principal criterion will be FEV1; the secondary criteria: quality of life, exacerbations requiring hospitalistion and mortality. EXPECTED RESULTS AND VIEWPOINTS: 300-500 patients are expected to be included. At the conclusion incorporation of this cohort into AIR (Alpha-antitrypsin International Registry) will increase the statistical power. This study could also provide the base for prospective trials and research projects.

Adolescent↗
PubMedDate not supplied

Inactivation of alpha 1-antitrypsin by aqueous coal solutions: possible relation to the emphysema of coal workers.

Increasing evidence demonstrates that emphysema in coal workers may be related to their exposure to coal dusts. The hypothesis that emphysema could be related to the production of reactive oxygen species (ROS) generated by inhaled coal dusts was examined in the present study. Using ESR, we investigated whether the interaction of different coals with dissolved oxygen in aqueous medium could generate ROS. Indeed, we found that one of the five examined French coal samples, Vouters coal, was effective in oxidizing formate anions or ethanol by a radical pathway. Inactivation of alpha 1-antitrypsin (alpha 1-AT) in vitro was then examined for all five coal filtrates. The Vouters coal filtrate, which exhibits oxidative activity, can also inactivate alpha 1-AT. When this coal filtrate was crystallized and redissolved, its oxidative activity was found to be conserved. By use of various analytical techniques, the active component of this coal filtrate was identified to be primarily ferrous sulfate. We confirmed that pure ferrous sulfate can effectively reduce oxygen to produce ROS in aqueous medium in vitro and can also inactivate alpha 1-AT. In this report, the nature of the coal-generated oxidative species, the origin of ferrous sulfate, and the stability of ferrous sulfate in the different coal samples are discussed. These results offer evidence that some inhaled coal dusts are capable of producing ROS, which may play an important role in the development of coal workers' emphysema.

Coal↗
PubMedDate not supplied

Factors that influence the formation and stability of hydrated ferrous sulfate in coal dusts. Possible relation to the emphysema of coal miners.

Epidemiological studies have shown that a causal relationship may exist between coal dust exposure and emphysema in coal miners. Emphysema can be considered as one of the human pathologies associated with oxidative stress, resulting from oxidant-induced alpha 1-antitrypsin (alpha 1-AT) inactivation and uncontrolled proteolysis of lung tissue. We have previously reported that certain coal dusts contained hydrated ferrous sulfate (FeSO4) that inactivated alpha 1-AT [Huang et al. (1993) Chem. Res. Toxicol. 6, 452-458]. In the present study, we have shown that the FeSO4 originated from oxidation of pyrite (FeS2), which is a typical contaminant of coal dusts. The relative humidity and microenvironment around individual pyrite particles influence the formation of FeSO4 in the coal. However, the subsequent human exposure to coal dust containing FeSO4 depends on the stability of the formed FeSO4. We found that pH played the most important role in stabilizing the FeSO4, such that a final pH < 4.5 after oxidation of pyrite stabilized FeSO4, whereas at high pH the conversion of reactive Fe2+ to Fe3+ was immediate. Sulfuric acid (H2SO4), which is also produced by the oxidation of pyrite, can lower the pH, but it can also be neutralized by other minerals in coal dusts, such as calcite (CaCO3). The stability of FeSO4 in coal dust can also be influenced by the length of exposure to air. Our studies demonstrated that coal samples differed in their capacity to stabilize FeSO4. This current study strengthens our previous reported hypothesis that emphysema, which occurs irregularly in coal miners, could be directly related to exposure to coal dust containing FeSO4.

Coal↗
PubMed2004

Psychological distress and depressed mood in employees with asthma, chronic bronchitis or emphysema: a population-based observational study on prevalence and the relationship with smoking cigarettes.

OBJECTIVES: To evaluate if employees with asthma, chronic bronchitis or emphysema can be characterized as a population of patients with a high prevalence of psychological distress and/or depressed mood. Above all, we wanted to examine the influence of smoking status on the relationship between chronic disease and psychological distress/depressed mood. METHODS: A postal survey was conducted among 12,103 employees participating in the Maastricht Cohort Study. RESULTS: Smoking employees, who reported having asthma, chronic bronchitis or emphysema were more likely to report suffering from depressed mood compared to smokers with no long-lasting disease (prevalence rate, PR: 29.3 and 9.0%, respectively; OR for depressed mood = 4.04; 95% CI: 2.56-6.39) and when compared to smoking employees with a history of heart disease, hypertension or myocardial infarction (PR: 18.1%; OR: 1.99; 95% CI: 1.07-3.68), or rheumatoid arthritis (PR: 20.1%; OR: 1.73; 95% CI: 0.96-3.11). CONCLUSION: These findings provide health care professionals with additional evidence regarding the importance for including the assessment of psychological distress and depressed mood in the routine evaluation of the patient with asthma, chronic bronchitis or emphysema, especially with regard to smoking cessation.

Age Distribution↗
PubMed2006

[Maxillary sinus infection with emphysema of the head as a "red herring" in steroid associated colon perforation].

Steroid therapy increases the risk of bowel perforation. Bowel perforation may occur at any time of steroid therapy, but the first weeks appear to hold the greatest potential for perforation. However, clinical findings after perforation may be misleading under steroids, and peritonitis may be absent. It is known that bowel perforation can lead to subcutaneous emphysema at various sites. Thus, in any patient with emphysema, bowel perforation must be included in the differential diagnosis, especially in patients receiving steroids. Missing knowledge of this entity may lead to marked delay between onset of initial signs and diagnosis, and hence worsen the survival rate. In this report we present a case of chronic steroid use, where asymptomatic sigma perforation led to a generalized emphysema, which was initially attributed to a maxillary sinus infection due to Aspergillus and anaerobic bacteria.

Aged, 80 and over↗
PubMed1999

Intrapulmonary gas mixing and the sloping alveolar plateau in COPD patients with macroscopic emphysema.

Chronic obstructive pulmonary disease patients, especially those with emphysema, show steep slopes of the alveolar plateau (S). This study tested the hypothesis that continued gas exchange between poorly and well-ventilated lung units by means of collateral ventilation would contribute to S in these patients. Nine young volunteers, nine older volunteers and 11 patients with macroscopic emphysema performed wash-out tests with helium (He) and sulphur hexafluoride (SF6). S was determined for breaths 1-5 (range 1), and for breaths between 95% and 98% of complete wash-out (range 2). An unequal ventilation index (UVI) was defined as the ratio between the estimated mean alveolar pressure and the end tidal pressure (PET) of each tracer gas, calculated over range 2. Over the same range, a phase III ratio was calculated by dividing PET by the estimated pressure at Fowler dead space. In all groups of subjects, the S for He and SF6 were greater for range 2 than for range 1 (p< or =0.012). In the emphysema patients, the correlations between S and UVI were 0.72 for He (p=0.012) and 0.81 for SF6 (p=0.002), while the mean phase III ratios were 1.7 for He and 2.4 for SF6, much less than their theoretical maxima. It was concluded that in patients collateral ventilation may account for only a small part of the increase in the alveolar plateau slope between ranges 1 and 2, and that this increase was mainly caused by unequal ventilation in combination with sequential emptying of lung units. The degree of sequential emptying, however, was modest compared with its full potential.

Adult↗
PubMed1999

Lung function after bilateral lower lobe lung volume reduction surgery for alpha1-antitrypsin emphysema.

This study explores the mechanism(s) of airflow limitation following lung volume reduction surgery (LVRS) in patients with emphysema due to homozygous alpha1-antitrypsin (AT) deficiency. Bilateral targeted lower lobe stapled LVRS using video thoracoscopy was performed in six patients (five males) aged 61+/-9 yrs (mean+/-SD) with alpha1-AT emphysema. Two patients received only a 6-month follow-up. However, four patients, at 22, 24, 27 and 36 months post-LVRS, noted relief from dyspnoea and increased walk tolerance. At 27+/-6 months (mean+/-SD) post-LVRS, their forced expiratory volume in one second improved only from 30+/-2% of the predicted value (mean+/-SEM) before surgery to 33+/-1% pred after surgery. Yet, total lung capacity (TLC) decreased from 151+/-13 to 127+/-10% pred; diffusing capacity increased from 35+/-9 to 59+/-9% pred; and vital capacity increased from 68+/-10 to 88+/-5% pred. In three patients, static lung elastic recoil at TLC increased from 1.1+/-0.15 to 1.2+/-0.10 kPa. Using flow/pressure curves, the mechanism for expiratory airflow limitation pre-LVRS and the improvement noted post-LVRS could be primarily accounted for by the initial loss and subsequent increase in lung elastic recoil. Bilateral lung volume reduction surgery provides modest physiologic improvement for 2-3 yrs in patients with alpha1-antitrypsin emphysema due to increases in lung elastic recoil.

Dyspnea↗
PubMed2000

Lung volume reduction surgery versus conservative treatment in severe emphysema.

Lung volume reduction surgery (LVRS) has been proposed for patients with severe emphysema to improve dyspnoea and pulmonary function. It is unknown, however, whether prognosis and pulmonary function in these patients can be improved compared to conservative treatment. The effect of LVRS and conservative therapy were compared prospectively in 57 patients with emphysema, who fulfilled the standard criteria for LVRS. The patients were divided into two groups according to their own decision. Patients in group 1 (n=29, eight females, mean+/-SEM 58.8+/-1.7 yrs, forced expiratory volume in one second (FEV1) 27.6+/-1.3% of the predicted value) underwent LVRS. Patients in group 2 (n=28, five females, 58.5+/-1.8 yrs, FEV1 30.8+/-1.4% pred) preferred to postpone LVRS. There were no significant differences in lung function between the two groups at baseline; however, there was a tendency towards better functional status in the control group. The control group had a better modified Medical Research Council (MMRC) dyspnea score (3.1+/-0.15 versus 3.5+/-0.1, p<0.04). Model-based comparisons were used to estimate the differences between the two groups over 18 months. Significant improvements were observed in the LVRS group compared to the control group in FEV1, total lung capacity (TLC), Residual volume (RV), MMRC dyspnea score and 6-min walking distance on all follow up visits. The estimated difference in FEV1 was 33% (95% confidence interval 13-58%; p>0.0001), in TLC 12.9% (7.9-18.8%; p>0.0001), in RV 60.9% 32.6-89.2%; p>0.0001), in 6-min walking distance 230 m (138-322 m; p<0.002) and in MMRC dyspnoea score 1.17 (0.79-1.55; p<0.0001). In conclusion, lung volume reduction surgery is more effective than conservative treatment for the improvement of dyspnoea, lung function and exercise capacity in selected patients with severe emphysema.

Adult↗
PubMed2002

Severity of elastase-induced emphysema is decreased in tumor necrosis factor-alpha and interleukin-1beta receptor-deficient mice.

A single intratracheal dose of porcine pancreatic elastase, which is cleared from the lung by 24 hours, was administered to wild-type, IL-1beta type 1 receptor-deficient, double TNF-alpha (type 1 and type 2) receptor-deficient, and combined TNF-alpha (type 1 receptor) plus IL-1beta receptor-deficient mice. The mean linear intercept (Lm) of saline-treated mice was 32(3) microm [mean(SE)]. For wild-type elastase-treated mice, Lm was 81(6) microm at 21 days versus 52(5) microm at 5 days after treatment, indicating that alveolar wall remodeling occurs long after the elastase injury. At 21 days, Lm values were 67(10), 62(3), and 39(5) microm in elastase-treated mice deficient in the IL-1beta receptor, double TNF-alpha receptors, and combined receptors, respectively. The level of apoptosis assessed by a terminal deoxynucleotidyl transferase-catalyzed in situ nick end-labeling assay was increased at 5 days after elastase treatment and was markedly and similarly attenuated in the IL-1beta, the double TNF-alpha, and the combined receptor-deficient mice. Our results indicate that inflammatory mediators exacerbate elastase-induced emphysema. We estimate that in the combined TNF-alpha + IL-1beta receptor-deficient mice, inflammation accounts for about 80% of the emphysema that develops after elastase treatment; decreased apoptosis of lung cells likely contributes to decreased severity of emphysema.

Analysis of Variance↗
PubMed2003

Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema.

Integrins are heterodimeric cell-surface proteins that regulate cell growth, migration and survival. We have shown previously that the epithelial-restricted integrin alpha(v)beta6 has another critical function; that is, it binds and activates latent transforming growth factor-beta (TGF-beta). Through a global analysis of pulmonary gene expression in the lungs of mice lacking this integrin (Itgb6 null mice) we have identified a marked induction of macrophage metalloelastase (Mmp12)--a metalloproteinase that preferentially degrades elastin and has been implicated in the chronic lung disease emphysema. Here we report that Itgb6-null mice develop age-related emphysema that is completely abrogated either by transgenic expression of versions of the beta6 integrin subunit that support TGF-beta activation, or by the loss of Mmp12. Furthermore, we show that the effects of Itgb6 deletion are overcome by simultaneous transgenic expression of active TGF-beta1. We have uncovered a pathway in which the loss of integrin-mediated activation of latent TGF-beta causes age-dependent pulmonary emphysema through alterations of macrophage Mmp12 expression. Furthermore, we show that a functional alteration in the TGF-beta activation pathway affects susceptibility to this disease.

Aging↗
PubMed1988

Muscle wasting in emphysema.

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using L-[1-13C]leucine. 2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered. 3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed. 4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

Adult↗
PubMed2003

Secretory leukocyte proteinase inhibitor, alpha-1-antitrypsin deficiency and emphysema: Preliminary study, speculation and an hypothesis.

OBJECTIVES: This study investigated (i) whether adequate concentrations of secretory leukocyte proteinase inhibitor (SLPI) in the lungs of alpha-1-antitrypsin (A1AT) deficient patients can explain the variability in the development of emphysema in these individuals, and (ii) whether cigarette smoking jeopardises the protective screen provided by functional SLPI. METHODOLOGY: Four subjects [two normal proteinase inhibitor M (PiM), two abnormal PiZ] were selected from patients presenting for diagnostic bronchoscopy and lung function testing (spirometry, DLco). Each subject underwent BAL and had blood taken for A1AT and SLPI estimation. RESULTS: As expected serum and BAL A1AT concentrations were within the normal range in the normal PiM subjects. In normal subjects, SLPI concentrations in serum and BAL were within the normal range. A1AT-deficient subjects had reduced serum and BAL levels of A1AT reflecting their genetic disorder but showed increased concentrations of SLPI in BAL and serum. Percentage neutrophil elastase (NE) inhibitory capacity of BAL fluid was low in both A1AT-deficient subjects and a cigarette-smoking normal subject. In contrast, the NE inhibitory capacity for the normal subject who had never smoked was normal. CONCLUSIONS: These findings suggest that in A1AT deficiency there may be a compensatory increase in SLPI. This may protect the lung against the development of emphysema in A1AT-deficient individuals. Cigarette smokers may have a lower SLPI concentration than non-smokers. This provides an explanation for at least some of the observed variation in the development of emphysema in A1AT deficient subjects.

Aged↗
PubMedDate not supplied

Massive subcutaneous emphysema following percutaneous tracheostomy.

BACKGROUND: Bronchoscopic subcutaneous dilatational tracheostomy is fast becoming the method of choice for securing an airway in chronic ventilated patients in an intensive care setting. Many studies have demonstrated that it is a cost-effective and safe procedure in experienced hands. Complications appear to be equivalent to those encountered in open tracheostomy. Subcutaneous emphysema following tracheostomy is a rare occurrence. Only 3 cases have been described following percutaneous dilatational tracheostomy. Management can be quite complex. MATERIAL AND METHODS: Retrospective review with case report of a patient with massive subcutaneous emphysema following percutaneous tracheostomy. CONCLUSION: Massive subcutaneous emphysema following percutaneous tracheostomy is a major complication that is rarely encountered. When due to a posterior tracheal wall tear, management consists of bypassing the laceration and allowing it to heal secondarily.

Aged↗
PubMed1998

German Thoracic Research Scholarship 1996: lung volume reduction for endstage pulmonary emphysema at the Washington University of St. Louis.

The Thoracic Research Scholarship 1996 of the German Society for Thoracic and Cardiovascular Surgery enabled me to visit Barnes Hospital at the Washington University of St. Louis, USA, from May to July 1996. At that center Prof. J. D. Cooper has established lung-volume reduction surgery as a successful surgical treatment for patients with endstage pulmonary emphysema. The operation is performed using left-sided double-lumen intubation. After opening of the chest and pleura and starting single-lung ventilation the less diseased parts of the second lung collapse due to absorption atelectasis whereas the more diseased portion of the lung stays hyperinflated. Linear staplers buttressed with bovine pericardium are used to resect the diseased parts of the lungs. Approximately 20-30% of the total lung volume can be resected by this way on each side. After inspection of the lungs for air leaks and preparation of pleural tents the pleura is closed bilaterally. Postoperative analgesia is performed via epidural catheter and patients are extubated postoperatively as soon as possible, usually in the operating theatre. 150 bilateral lung-volume reduction procedures for patients with severe emphysema were performed between January 1993 and February 1996 in St. Louis. 6 months postoperatively the 1-second forced expiratory volume had increased by up to 51% and residual volume was reduced by 28%. 70% of patients who required continuous oxygen supply prior to the operation no longer required this measure: the PaO2 had increased by an average of 8 mmHg. These data demonstrate that bilateral lung-volume reduction surgery is a suitable treatment for patients with terminal pulmonary emphysema. Most important for the success of this procedure are clear selection and specific perioperative treatment of the patients.

Animals↗
PubMed1998

[Value of orally administered retard morphine for therapy of severe pulmonary emphysema of the pink-puffer type. A pilot study].

BACKGROUND AND OBJECTIVE: In severe "pink puffer" emphysema the patients' physical capacity is limited by dyspnoea despite maximal application of established treatment. This pilot study investigated the effect of retarded morphine, taken orally for 10 days, on ventilation, dyspnoea, walking capacity and wakefulness. PATIENTS AND METHODS: Twenty clinically stable patients (11 men, 9 women, mean age 68.5 [50-81] years) with "pink puffer" emphysema were studied over a period of 10 days in a prospective, non-controlled trial of cross-over design. Criteria for inclusion in the study were: 1-second forced expiratory volume (FEV1) < 1 I, vital capacity < 50% and normocapnia. In addition to their existing therapy patients received either no further therapy or retarded morphine. Morphine dosage was increased to maximally 3 x 30 mg daily, depending on effectiveness and side effects, dyspnoea at rest and immediately after a 6-min walk (assessed with Borg's visual analog scale), maximal walking capacity were determined, as well as blood gases, respiratory minute volume and the respiratory drive (airway occlusion pressure [P0.1]), responsiveness of the respiratory pathways to CO2 and wakefulness (concentration, fatigue, interest in surroundings). RESULTS: Twelve patients completed the study (group A). In the remaining patients (group B) the test had to be stopped prematurely because of undesirable side effects or an exacerbation of the underlying infection. In group A, morphine (mean dosage: 49.2 +/- 28.4 mg/d) caused a reduction of PaO2, dyspnoea on activity, the resting minute respiratory volume, respiratory drive and CO2 response, and an increase in PaCO2, HCO3- and the 6-min walking distance. Morphine did not produce a change in subjectively evaluated vigilance and the blood pH. CONCLUSION: After strict patient selection oral morphine produced a reduction of exercise dyspnoea and an increase in walking capacity in half of the patients with severe pulmonary emphysema. There also occurred a slight rise in PaCO2 without any relevant respiratory acidosis or significant decrease in wakefulness.

Administration, Oral↗
PubMedDate not supplied

[Lobar emphysema. Important differential diagnosis of obstructive lung diseases in childhood].

The lobar emphysema is characterised by a lobe-restricted overinflation combined with dislocation of the neighbouring organs. Surgical treatment is indicated because of the high mortality by waiting and conservative treatment. Differential diagnosis has to exclude other causes for overinflation as atelectasis with compensated emphysema, diaphragmatic hernia, and stenotic changing of the tracheobronchial tree and others. In the course of a retrospective study of 6350 thoracotomies (1978-1988) out of 198 patients with congenital malformations of the lungs 5 (2.5%) children less than 5 years were found to have undergone surgical therapy because of lobar emphysema. Five patients were found with additional malformations in four patients this was held to be the cause. All patients were dyspnoeic at the time of operation. The most important diagnostic procedure was the routine x-ray of the chest and fluoroscopic examination. In 4 patients surgical treatment consisted in lobectomy, in one patient segmental resection was sufficient. There was no 30-day-mortality, postoperative recovery was uneventful in all patients.

Child↗
PubMed1999

Unilateral pulmonary interstitial emphysema following pneumonia in a preterm infant successfully treated with prolonged selective bronchial intubation.

We describe a ventilated preterm infant (26 week's gestation) who developed severe right-sided pulmonary interstitial emphysema following Staphylococcus aureus pneumonia. Prolonged selective bronchial intubation (10 days) resulted in a marked clinical improvement and resolution of the emphysema. Resolution of unilateral pulmonary interstitial emphysema may require a longer course of selective bronchial intubation than currently recommended.

Bacteremia↗
PubMed1984

Diagnosis of emphysema on chest radiographs.

To evaluate how well pulmonary emphysema could be diagnosed on routine chest radiographs by using generally known criteria, a radio-pathologic correlative study was performed in 88 unselected patients with post-mortem verification of emphysema. The signs used were: I. Signs of overinflation as (a) blunting of the costophrenic sinuses and/or depression of the dome of the right diaphragm, (b) widening of the retrosternal airspace and (c) a right or obtuse sternodiaphragmatic angle, II. Irregular radiolucencies. III. Arterial deficiency. If two or more of the above signs were present, a total accuracy of 77% in detecting emphysema was achieved. The irregular radiolucency and arterial deficiency signs were sensitive but less accurate than those of overinflation.

Adult↗