Pathophysiology and treatment of alpha 1-antitrypsin deficiency

The pathophysiology of alpha 1-antitrypsin (AAT) deficiency and the use of alpha 1-proteinase inhibitor therapy in the management of emphysema caused by AAT deficiency are described. AAT deficiency is the most common genetic cause of liver disease in children and emphysema in adults. However, not all patients with AAT deficiency develop hepatic or pulmonary involvement. Changes in the composition of the AAT molecule have been associated with AAT dysfunction in liver disease, whereas lung disease occurs when AAT concentrations are reduced. A definitive diagnosis can be made through serum AAT phenotype determination. Therapy for liver disease induced by AAT deficiency consists of supportive measures. Therapy for pulmonary disease due to AAT deficiency includes AAT augmentation therapy along with supportive measures. The available product, alpha 1-proteinase inhibitor, is derived from fractionated plasma and has similar biological activity to native serum AAT. Clinical trials have demonstrated a positive effect on serum and lung concentrations of AAT with few adverse events. Two recombinant forms of AAT have also been developed; however, few trials have been published evaluating their safety and efficacy in AAT-deficient patients. Many questions remain unanswered concerning AAT deficiency and replacement therapy. AAT augmentation therapy appears to reduce the progression of emphysema in some AAT-deficient patients.     

Latex hypersensitivity/glove component reaction as a contributing factor to osteomyelitis of the hand: a case report and review of the literature

High-resolution computed tomography (HRCT) can be used to diagnose and quantify emphysema noninvasively, as significant correlations have been found between the histological grade on resected lung specimens and quantified (q) computed tomography (CT). In this study, we performed thin section qHRCT in patients with severe hereditary alpha-1-antitrypsin (AAT) deficiency. AAT deficiency is the most common genetic cause of emphysema in adults, and exercise intolerance is the most disabling, distressing consequence of emphysema for the majority of patients. qHRCT was used to quantify precisely the alterations in the lung parenchyma due to pulmonary emphysema. Up until now, the important relationship between the severity of emphysema and the reduced exercise capacity has received little attention. Therefore the purpose of the study was to investigate the relationship between emphysema as displayed by qHRCT and cardiopulmonary exercise testing (CPX) in patients with severe cardiopulmonary impairment. - qHRCT was performed in 21 patients with homozygous AAT deficiency. CT scans were obtained at three spirometrically standardized levels at the carina and (5 cm above and below the carina). The mean lung density at 50% of vital capacity and a quantitative histogram analysis of the frequencies of CT values were determined. All patients underwent symptom-limited CPX to analyse simultaneously cardiovascular and ventilatory systems responses. - In all patients, qualitative CT assessment demonstrated panlobular emphysema with large and extensive areas of uniform low attenuation, characteristically with a lower-lobe distribution. Mean CT density values of the patients (-845 +/- 6.9 (mean +/- SEM)) were significantly correlated with work capacity (r = 0.55, p <0.01), oxygen-pulse (r = 0.54, p <0.01) and functional dead space ventilation (r = -0.54, p <0.01). Moreover, severe emphysema index (CT values below a threshold value of 950 HU) correlated positively with functional dead space ventilation (r = 0.60, p <0.01) and alveolar-arterial oxygen difference (r = 0.70, p <0.001). - These results clearly demonstrate that CPX parameters, indicating a disturbed pulmonary gas exchange and a ventilation-perfusion-mismatch during exercise, are significantly related to the extent of lung emphysema.     

Alpha 1-antitrypsin deficiency and asthma. The continuing search for the relationship

Patients with alpha 1-antitrypsin (AAT) deficiency, like those with asthma and chronic obstructive pulmonary disease, usually present with dyspnea, wheeze, and cough. The similarity in presentation and unfamiliarity among clinicians with AAT deficiency account for much of the delay in diagnosis. Normally, AAT inhibits serine proteases, which cause alveolar destruction, and alters the function of cells that release mediators of inflammation. Diagnostic findings suggesting deficiency include irreversible airflow obstruction, a decreased diffusing capacity of the lung for carbon monoxide, bibasilar bullous disease on chest films, and a low serum level of AAT. Asthma is usually diagnosed on the basis of clinical findings and response to inhaled beta agonists. The presence of inflammation is believed to be necessary for development of clinically significant asthma. Inflammation added to a deficiency of antiprotease inhibitor activity significantly worsens bronchial hyperreactivity. This is only one mechanism by which AAT deficiency may potentiate allergic and bronchospastic responses. The prevalence of bronchial asthma in patients with AAT deficiency is unknown. Studies by the National Institutes of Health regarding the natural history of AAT deficiency and its response to therapy are under way. Perhaps more will be discovered about the relationship between the disorder and bronchial asthma.     

Lung volume reduction surgery for severe emphysema

BACKGROUND: We report mid-term results after 25 consecutive lung volume reduction operations (LVRS) for the treatment of severe dyspnea due to advanced emphysema. METHODS: Study design: patients were studied prospectively up to 12 months after surgery. Setting: preoperative evaluation, surgery and postoperative care took place in our university hospital. Patients: patient selection was based on severe dyspnea and airway obstruction despite optimal medical treatment, lung overinflation and completed rehabilitation programme. Patients with severe hypercarbia (PCO2>50 mmHg) were excluded. Nineteen rehabilitated patients who fulfilled our inclusion criteria but postponed or denied LVRS were followed up clinically. Interventions: LVRS was performed bilaterally in 22 patients (median sternotomy) and unilaterally in 3 patients (limited thoracotomy). Measures: Outcome was measured by dyspnea evaluation, 6-minute-walking distance and pulmonary function tests. RESULTS: Twelve months postoperatively dyspnea and mobility improved significantly (MRC score from 3.3+/-0.7 to 2.12+/-0.8, 6-min-walk from 251+/-190 to 477+/-189 m). These results were superior compared to the results of the conservatively treated patients. Significant improvement could also be documented in airway obstruction (FEV1 from 960+/-369 to 1438+/-610 ml) and overinflation (TLC from 133+/-14 to 118+/-21% predicted and RV from 280+/-56 to 186+/-59% predicted). CONCLUSIONS: LVRS is an effective and promising treatment option for selected patients with end-stage emphysema and could be offered as an alternative and / or bridge to lung transplantation.     

Radiologic emphysema morphology is associated with outcome after surgical lung volume reduction

BACKGROUND: Lung volume reduction surgery is known to alleviate dyspnea and to improve pulmonary function, performance in daily activity, and quality of life in selected patients with severe pulmonary emphysema. We investigated the role of radiologically assessed emphysema morphology on functional outcome after a lung volume reduction operation. METHODS: The preoperative chest computed tomograms in 50 consecutive patients who had undergone surgical lung volume reduction were retrospectively reviewed by 6 physicians blinded to the clinical outcome. Emphysema morphology was determined according to a simplified classification (ie, homogeneous, moderately heterogeneous, and markedly heterogeneous; lobe predominance). We studied the impact of these morphologic aspects on functional outcome at 3 months. RESULTS: We found a fair interobserver agreement applying our classification system. Functional improvement after surgical lung volume reduction was best in markedly heterogeneous emphysema with an increase in forced expiratory volume in 1 second of 81% +/- 17% (mean +/- standard error, n = 17) compared with 44% +/- 10% (n = 16) for intermediately heterogeneous emphysema. But also in patients with homogeneous emphysema clinical relevant improvement of function could be observed (increase in forced expiratory volume in 1 second = 34% +/- 6%; n = 17). CONCLUSIONS: The morphologic type of emphysema, assessed by a simplified surgically oriented classification, is an important predictor of surgical outcome. Lung volume reduction surgery may also improve dyspnea and lung function in homogeneous emphysema.     

Thoracoscopic bilateral lung volume reduction for diffuse pulmonary emphysema

OBJECTIVE: In a prospective study, we investigated the functional results, complications and survival of bilateral video-assisted thoracoscopic (VAT) lung volume reduction (LVR) in a selected group of patients with severe, nonbullous pulmonary emphysema. From January 1994 to September 1996, 42 of 143 candidates (13 female, 29 male, 42-78 years) were operated. They were short of breath on minimal exertion due to severe airflow obstruction and hyperinflation (FEV1 < 30%) pred., TLC > 130% pred., RV > 200% pred.). METHODS: LVR was performed bilaterally by VAT using endoscopic staplers without buttressing the staple lines. Pulmonary function test (PFT), MRC dyspnea score and 12 min walking distance were assessed preoperatively, at 3, 6 and 12 months. In addition lung function was measured at hospital discharge. RESULTS: The patients reported a marked relief of dyspnea, which persisted at all follow-up visits (P<0.001). FEV1 increased from 0.80 +/- 0.24 (L) to 1.14 +/- 0.41 (L) postoperatively, a 43% gain (P < 0.001). A relevant increase of FEV1 persisted for at least 1 year. The residual volume to total lung capacity ratio decreased from 0.64 to 0.56 at hospital discharge. The mean 12 min walking distance increased from 500 +/- 195 (m) to 770 +/- 222 (m) after 1 year (P < 0.001). The mean hospital stay was 13 +/- 5.5 days (median 12.0), drainage time was 9 +/- 4.3 (median 8.0) days. There was no 30 day mortality. Three patients died between 2 and 15 months postoperatively by non surgery related reasons. One patient underwent lung transplantation 5 months after surgical lung volume reduction. CONCLUSIONS: In a selected group of patients with severe, nonbullous pulmonary emphysema, bilateral LVR by VAT results in instantaneous postoperative improvement in pulmonary function and dyspnea. These favorable effects, including an amelioriation in exercise performance, lasted for at least 1 year.     

Arterial carbon dioxide tension and dyspnea in chronic bronchitis and pulmonary emphysema

The severity of dyspnea (MRC scale) was confronted to the blood carbon dioxide tension (PaCO2) in 45 patients with chronic nonspecific lung disease having moderate or severe airway obstruction (FEV1.0 of less than 1.5 liters). The patients were classified as "bronchitic", "emphysematous" and "intermediate" using a 10- criterion (clinical, roentgenologic and biological) "emphysema score". No correlation between dyspnea grade and PaCO2 was found in "bronchitic" and "intermediate" patients; in the "emphysematous" subgroup PaCO2 tended to rise as dyspnea was more severe, but the linear correlation coefficient (r= +0.37) did not reach the significance threshold, which is high (0.468) for such a limited number of observations.     

Surface expression and release of soluble forms of CD8 and CD23 in CD40- and IL-4-activated mononuclear cells from patients with Graves'' disease (GD)

OBJECTIVE: This study was performed to assess the usefulness of preoperative thin-section CT alone and in combination with physiologic measurements in emphysema patients being evaluated for lung volume reduction surgery. SUBJECTS AND METHODS: Six 1-mm collimation sections through the chest were obtained in 20 patients being evaluated for lung volume reduction surgery. Extent and severity of emphysema were assessed by visually scoring the images. CT scores ranged from 0 to 144. Inspiratory resistance was measured in 12 of 20 patients and was also used to discriminate between responders (change in forced expiratory volume in 1 sec, > or = 150 ml after surgery) and nonresponders (change in forced expiratory volume in 1 sec, < 150 ml after surgery). RESULTS: Four of 20 patients with mild emphysema as revealed by thin-section CT (scores of < 50) did not improve lung function after lung volume reduction surgery. Eight of the remaining 16 patients with moderate to severe emphysema as revealed by thin-section CT (scores of > 50) underwent inspiratory resistance measurement. Those seven patients whose inspiratory resistance measurement exceeded 8.5 cm H2O/l per second did not respond favorably to lung volume reduction surgery (change in forced expiratory volume in 1 sec, < 150 ml). The remaining five patients whose inspiratory resistance measurement was less than 8.5 cm H2O/l per second responded favorably to lung volume reduction surgery. Thus, only five of the 20 patients showed improvement in forced expiratory volume in 1 sec after surgery. CONCLUSION: Our data suggest that among patients with moderate to severe emphysema who are being examined for lung volume reduction surgery, the combination of radiologic and physiologic assessment is more accurate for predicting a favorable response to lung volume reduction surgery than radiologic assessment alone. However, in patients with chronic obstructive pulmonary disease by the American Thoracic Society criteria, mild emphysema as revealed on thin-section CT virtually precludes further workup because these patients are unlikely to respond favorably to lung volume reduction surgery.     

Clinical relevance of thiamine status amongst hospitalized elderly patients

BACKGROUND: The prevalence and the consequences of thiamine deficiency among elderly patients admitted to acute geriatric wards are not known. OBJECTIVES: (1) To assess the prevalence of thiamine deficiency in patients admitted to a geriatric ward compared to age-matched ambulatory outpatients; (2) to identify their diseases and problems associated with thiamine deficiency, and (3) to determine the relationship between the thiamine status and the cognitive and functional status of these patients. MATERIALS AND METHODS: 118 aged hospitalized patients (83 +/- 7 years; mean age +/- SD) were prospectively enrolled on admission to the geriatric ward. Their cognitive status was assessed using the Mini-Mental State Examination (MMSE) and their ability to perform their activities of daily living (ADL) using ADL scales. The effect of exogenous thiamine pyrophosphate (TPP) addition on the blood transketolase (TK) activity (TPP TK effect) served to estimate thiamine deficiency. Socioeconomic data, diseases and treatment were identified as potential associated risk factors. This group of hospitalized patients was divided according to their thiamine status to characterize the conditions associated with thiamine deficiency. Thirty-five outpatients without any functional or cognitive impairment served as a control group. RESULTS: Of 118 inpatients, 46 (39%) presented with a TPP TK effect of >15%, and 6 with values of >22%, indicating moderate and severe thiamine deficiency, respectively. Only 6 of 30 outpatients (20%) exhibited a TPP TK effect of >15% and none of them reached values of >18%. Although it tended to be lower in outpatients, the mean TPP TK effect did not statistically differ from the mean of inpatients. Thiamine-deficient inpatients comprised a larger proportion of institutionalized subjects than nondeficient inpatients (87 versus 47%, p < 0.001). Functional status, cognitive functions and the occurrence of delirium did not differ according to their thiamine status. By contrast, thiamine-deficient inpatients exhibited a higher proportion of Alzheimer's disease, depression, cardiac failure and falls. Furosemide was more frequently taken by thiamine-deficient patients. CONCLUSIONS: Severe thiamine deficiency remained quite low among the hospitalized elderly. The prevalence of moderate thiamine deficiency approached 40%. Institutionalized subjects were at particular risk of developing thiamine deficiency. Its clinical relevance on functional status and on cognitive function remained not significant. By contrast, a high proportion of falls, Alzheimer's disease, depression, cardiac failure and furosemide use could have been related to thiamine deficiency.     

Appetite suppressant drugs as inhibitors of human cytochromes P450: in vitro inhibition of P450-2D6 by D- and L-fenfluramine, but not phentermine

BACKGROUND: We compared our results with bullous vs diffuse emphysema by performing a bilateral thoracoscopic stapled volume reduction technique in 15 patients (age 45-80, 10 males, five females). METHODS: Eight patients demonstrated bullous emphysema and seven patients diffuse emphysema. Lung reduction was performed with a bilateral thoracoscopic stapled technique utilizing bovine pericardium in the supine position. RESULTS: Comparison of the bullous versus diffuse groups revealed no significant differences in means for the following variables: length of air leak (7.5 vs 3.3 days); length of stay (8.1 vs 6.5 days); pre-op FEV1, (23% vs 22%); pre-op dyspnea index (3.4 vs 3.6). At 3 months the bullous subset had a highly significant improvement (p < 0.007) in FEV1 (88%) compared with the diffuse subset FEV1 (59%). CONCLUSIONS: These early results suggest that patients with bullous emphysema are at no greater risk and demonstrate a significantly greater improvement in FEV1 than patients with diffuse emphysema.     

Hyperplasia of pulmonary neuroendocrine cells in a case of childhood pulmonary emphysema

Pulmonary emphysema is very uncommon in children in the first decade of life. The few cases documented in the literature were all due to alpha1-antitrypsin deficiency. We present the case of a 6-year-old white boy with chronic cough and dyspnea on exertion. Lung biopsy showed panacinar type emphysema with patent airways and diffuse hyperplasia of pulmonary neuroendocrine cells revealed after immunostaining for bombesin, a peptide produced by these cells. We speculate that idiopathic diffuse hyperplasia of bombesin-producing pulmonary neuroendocrine cells may contribute to the pathogenesis of unusual COPD in childhood.     

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.     

The sensitivity of hyaluronan analysis of pleural fluid from patients with malignant mesothelioma and a comparison of different methods

This retrospective chart review describes the efficacy and safety of long-term administration of intravenous alpha1-antitrypsin (AAT) in 14 patients with hereditary AAT deficiency and COPD. During the 12- to 48-month observation period, 12 to 14 patients had stabilization of functional status; 4 patients had reductions in hospitalizations. Thirteen of 14 patients had no decline in pulmonary function. Three patients had self-limited adverse reactions to the AAT with one patient requiring a brief hospitalization.     

Long-term therapy of alpha 1-antitrypsin-deficiency-associated pulmonary emphysema with human alpha 1-antitrypsin

alpha 1-antitrypsin (alpha 1-AT) deficiency is a genetic disorder characterized by low serum levels of alpha 1-AT and a high risk of pulmonary emphysema at a young age. The resulting surplus of proteases, mainly of neutrophil elastase, can be balanced by i.v. augmentation with alpha 1-AT. However, it is not clear if affected patients benefit from long-term augmentation therapy and no long-term safety data are available. We examined 443 patients with severe alpha 1-AT deficiency and pulmonary emphysema receiving weekly i.v. infusions of 60 mg/kg body weight alpha 1-AT in addition to their regular medication. The progression of the disease was assessed by repeated lung function measurements, particularly the decline in forced expiratory volume in 1 second (delta FEV1). 443 patients with alpha 1-AT deficiency tolerated augmentation therapy well with few adverse reactions. The delta FEV1 in 287 patients with available follow-up data was 57.1 +/- 31.1 ml per year. Stratified for baseline FEV1, the decline was 35.6 +/- 21.3 ml in the 108 patients with an initial FEV1 < 30% and 64.0 +/- 26.4 ml in the 164 with 30% < FEV1 < or = 65% of predicted normal (p = 0.0008). The remaining 15 patients had an initial FEV1 > 65%. Long-term treatment with i.v. alpha 1-antitrypsin in patients with severe alpha 1-Pi deficiency is feasible and safe. The decline in forced expiratory volume in one second is related to the initial forced expiratory volume in one second as in alpha 1-antitrypsin deficient patients not receiving augmentation therapy.     

Canine filarial infections in north Taiwan

STUDY OBJECTIVES: Define the incidence of obstructive atelectasis in patients presenting with small cell lung cancer and their response to treatment. DESIGN: Retrospective review of clinical records and radiographic studies. SETTING: Single federal government institution-the National Cancer Institute-Naval Medical Oncology Branch. PATIENTS: One hundred seventy-two consecutive patients treated between 1983 and 1993. INTERVENTIONS: Patients presenting with obstructive atelectasis were identified. The incidence of dyspnea, cough, and sputum production before starting treatment and 1, 3, and 6 months later was determined. Fiberoptic bronchoscopy and chest radiographs performed before starting treatment were compared with those obtained later in the patients' clinical course. MEASUREMENTS AND RESULTS: Thirty-seven of 172 (22%) patients had obstructive atelectasis. Initial symptoms included cough in 25 (68%), dyspnea in 24 (65%), and productive cough in 10 (27%). The patients' symptoms of cough, dyspnea, and sputum production decreased to one third of the initial prevalence 1 month after the start of treatment. Fiberoptic bronchoscopy and chest radiographs performed 3 months after starting treatment demonstrated bronchial patency in 90%. CONCLUSIONS: Obstructive atelectasis occurs in approximately one fifth of patients presenting with small cell lung cancer. Chemotherapy and chemotherapy plus chest radiotherapy lead to symptomatic, bronchoscopic, and radiographic resolution in similar proportions of patients with obstructive atelectasis.     

Assessment of complications in patients with lung transplantation with high resolution computerized tomography

INTRODUCTION: High Resolution Computed Tomography (HRCT) has been used by many authors to study the early complications of lung transplantation. Bronchoscopy, transbronchial biopsy and the clinical parameters are the tools of choice to diagnose such complications; HRCT showed excellent sensitivity (100%) and good specificity (93%) especially in detecting bronchial stenoses. We report the preliminary results of HRCT in detecting early/late complications in lung transplant recipients. MATERIAL AND METHODS: Sixteen lung transplant recipients (5 single and 11 double transplants) were examined with HRCT at the Servizio Speciale Diagnostica V of "La Sapienza" University (Rome, Italy). The CT findings were compared with the results of bronchoscopy and respiratory function tests. The patients (8 men and 8 women; age range: 18-57 years, mean: 37.5) had cystic fibrosis (9), emphysema (3), alpha-1-antitrypsin deficiency (1), idiopathic pulmonary fibrosis (2), and bronchiectasis (1). RESULTS AND DISCUSSION: During the follow-up, one patient died of pulmonary edema. CT findings were normal in 3 patients and mild pleural effusion was seen in 2. The other HRCT findings were: bronchial stenosis in 5 cases (which was bilateral in 1) and bronchial dehiscence in 1 patient; four cases of infection (1 CMV, 1 aspecific bacterial pneumonia, 1 Chlamydia psittacea and 1 Aspergillosis) and one of brochiolitis obliterans. A patient was treated for acute and one for chronic rejection. A CMV infection involved only the native lung in a patient. CT is easy to perform and a repeatable and well-tolerated tool with high sensitivity (100%) and good specificity (93%) in the early diagnosis of complications, particularly bronchial stenoses, which complications are often missed at bronchoscopy or clinically silent. CT should be always performed before bronchoscopy because it can provide valuable information for bronchoscopy targeting. CONCLUSIONS: In agreement with other authors we consider HRCT a very useful tool in the early diagnosis of the complications following lung transplantation.     

Osteomyelitis of the foot: relative importance of primary and secondary MR imaging signs

STUDY OBJECTIVES: Dyspnea is most commonly assessed by questioning patients about their subjective perception of shortness of breath during physical exertion. Although speech production is altered by pulmonary disease, it has not been included in current dyspnea assessment tools. A questionnaire was developed to address reports of dyspnea during (1) physical activity, (2) speech activity, and (3) simultaneous speech and physical activity. DESIGN: An equal number of self- and experimenter-administered 30-item questionnaires was given to 203 patients with restrictive and obstructive pulmonary diseases. Their responses were analyzed statistically. RESULTS: The questionnaire had high internal consistency for individual items within each of the three sections. The sections were highly correlated but provided separate and distinct information. Factors extracted from each section were related to severity of dyspnea. Pairwise t tests demonstrated highly significant differences in subject responses to the three sections. The least dyspnea was experienced during speech activities, more during physical activities, and the most when speech and physical activities were combined. CONCLUSIONS: The questionnaire proved to be a quickly administered tool for providing information about the effect of dyspnea on activities of daily living. Because of the emphasis on dyspnea during speech production, it may be particularly useful for assessing patients who rely extensively on speaking ability for their livelihood.     

Pulmonary vein stenosis after catheter ablation of atrial fibrillation

BACKGROUND: This report describes the complication of pulmonary vein stenosis with resultant severe pulmonary hypertension that developed in 2 patients after successful catheter ablation of chronic atrial fibrillation. METHODS AND RESULTS: Three months after successful catheter ablation of atrial fibrillation, both patients developed progressive dyspnea and pulmonary hypertension. Both were found to have severe stenosis of all 4 pulmonary veins near the junction with the left atrium. Balloon dilation of the stenotic pulmonary veins was performed in these patients, with improvement in dyspnea and pulmonary hypertension. CONCLUSIONS: The complication of pulmonary vein stenosis is potentially life-threatening, and the application of radiofrequency current within the pulmonary veins with standard catheter technology should be avoided. This complication can be treated with balloon dilation, although the long-term course is unknown.     

Usefulness of a national registry of alpha-1-antitrypsin deficiency. The Spanish experience

Severe alpha-1-antitrypsin (AAT) deficiency, phenotype Pi ZZ, is a rare condition with an estimated prevalence of 1/4500 individuals in Spain. Given this low prevalence, it seems useful to accumulate all the information derived from the care of these patients. In this context, the Spanish Registry of patients with AAT deficiency was founded in 1993; its main objectives were to establish guidelines adapted to our country for the treatment and management of AAT-deficient patients, offer expert support to physicians all over the country treating these patients, and provide technical support on the determination of Pi phenotyping and genotyping of individuals suspected of being AAT-deficient. From 1993 to January 1998 the number of enrollees increased from 48 to 223, of which 216 were Pi ZZ. Seventy-three per cent were male and only 31.5% were never smokers, mean age was 46 years (SD = 13 years) and mean FEV1 53% predicted (SD = 31%). 83% were index cases who, compared with non-index cases, were older (49 +/- 11 vs. 35 +/- 13 years, P < 0.001), more likely to have a smoking history (85% vs. 47%, P < 0.01) and displayed more severe impairment in pulmonary function (FEV1% = 40% +/- 19% vs. 96% +/- 23%, P < 0.001). Augmentation therapy was administered to 129 patients (58%). Treated patients had more severe impairment in pulmonary function than the untreated (FEV1% = 40% +/- 21% vs. 72% +/- 32%, P < 0.001) and were more likely to be index cases (81% vs. 43%, P < 0.001). Characteristics of the patients included are similar to those described for other Registries. The Registry has extended knowledge of the disease throughout the country and has established local guidelines for treatment and follow-up. It may be a valid database for future co-operation in international initiatives.     

Surgical treatment of advanced lung emphysema. Does it really improve treatment results?

Lung emphysema may be one of the components of chronic obstructive pulmonary disease (COPD). Nearly 60% of patients with advanced chronic respiratory insufficiency with FEV1 < 30% expected, aged > 65 years die within the first 2 years of the disease. The treatment of COPD includes oxygen therapy, lung transplantation and/or lung volume reduction (LVR). The study presents qualification criteria for LVR in reference to oxygen therapy and lung transplantation. Crucial diagnostic features include: CT of the chest with densitometric analysis and lung perfusion scans. Patients with severe but limited dyspnea, disseminated emphysema lesions with fairly untouched areas of normal lung tissue, FEV1% < 30-35%, DLCO < 25% expected, PaCO2 < or = 50 mmHg and PaO2 < or = 50-55 mmHg, appear to be the best candidates for LVR. The results of the study indicate, that in Poland, patients with advanced emphysema, who are treated with oxygen therapy or soon will be qualified this therapy or await lung transplantation might be candidates for LVR. The early results of lung volume reduction are promising and include: decrease in total lung capacity, residual volume and breathing frequency. LVR has been in use for about 3 years and majority of authors still do not possess clinical observations long enough to obtain statistically significant comparison with other methods of treatment. Limited morbidity and low perioperative mortality enable application of LVR even in patients with severe respiratory insufficiency and/or requiring constant oxygen therapy. In conclusion considering all positive aspects of LVR it is necessary to emphasise that for overall assessment of this method a broader clinical material is required including data on duration of clinical improvement.