New Patient-Centric Approaches to the Management of Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed genetic predisposition for COPD and emphysema and other conditions, including liver disease. Although there have been improvements in terms of awareness of AATD and understanding of its treatment in recent years, current challenges center on optimizing detection and management of patients with AATD, and improving access to intravenous (IV) AAT therapy - the only available pharmacological intervention that can slow disease progression. However, as an orphan disease with geographically dispersed patients, international cooperation is essential to address these issues. To achieve this, new European initiatives in the form of the European Reference Network for Rare Lung Diseases (ERN-LUNG) and the European Alpha-1 Research Collaboration (EARCO) have been established. These organizations are striving to address the current challenges in AATD, and provide a new platform for future research efforts in AATD. The first objectives of ERN-LUNG are to establish a quality control program for European AATD laboratories and create a disease management program for AATD, following the success of such programs in the United States. The main purpose of EARCO is to create a pan-European registry, with the aim of understanding the natural history of the disease and supporting the development of new treatment modalities in AATD and access to AAT therapy. Going further, other patient-centric initiatives involve improving the convenience of intravenous AAT therapy infusions through extended-interval dosing and self-administration. The present review will discuss the implementation of these initiatives and their potential contribution to the optimization of patient care in AATD.

Role of Stem Cells in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Pulmonary Emphysema.

There are only few human translational studies performed in the area of stem cell research in patients with chronic obstructive pulmonary disease (COPD) and/or pulmonary emphysema. Before progress to clinical trials with stem cells we strongly believe that more human translational studies are essential, otherwise, the clinical rationale would be solely based on limited in vitro and animal studies. In the future, stem cell therapy could be a treatment for this incurable disease. As of now, stem cell therapy is still to be considered as an area of active research, lacking any strong rationale for performing clinical trials in COPD. Although stem cells would be likely to represent a heterogeneous population of cells, the different cell subsets and their importance in the pathogenesis of the different clinical phenotypes need to be fully characterised before progressing to clinical trials. Moreover, the potential side effects of stem cell therapy are underestimated. We should not ignore that some of the most deadly neoplasms are arising from stem cells.

Acupuncture Treatment for Dyspnea due to Combined Pulmonary Fibrosis and Emphysema: A Case Report.

OBJECTIVE: Combined idiopathic pulmonary fibrosis with pulmonary emphysema (CPFE) is a syndrome with a characteristic presentation of upper lobe emphysema and lower lobe fibrosis. Dyspnea on exertion (DOE) is a major symptom of CPFE. We report a patient with DOE due to CPFE who was successfully treated with acupuncture. DESIGN: Case report. CASE PRESENTATION: A 72-year-old Japanese man with a 4-year history of DOE was diagnosed with CPFE 2 years previously in another hospital. He received standard Western medicine treatment, which included bronchodilators. However, his DOE did not improve. Consequently, he visited our hospital for acupuncture treatment and received acupuncture treatment once a week for 1 year. RESULTS: After 10 weeks of acupuncture treatment, the results of the 6-minute walk test (6-minute walking distance, 379 m; lowest oxygen saturation, 86%; modified Borg dyspnea scale score: 2 units) were better than those at baseline (352 m, 84%, 4 units, respectively). These values were sustained at both 30 weeks (470 m, 88%, 1 unit) and 60 weeks (473 m, 85%, 2 units). Serum interstitial biomarkers, Krebs von den Lungen and surfactant protein-D, decreased after commencement of acupuncture therapy. CONCLUSION: A patient with CPFE showed improvements in dyspnea scores, exercise tolerance, and serum biomarkers during a 1-year course of acupuncture treatment. Use of acupuncture might be an effective adjunct therapy in relieving DOE due to CPFE. A large, well-designed cohort study that includes patients with CPFE treated with acupuncture should be conducted.

Novel aspects of pathogenesis and regeneration mechanisms in COPD.

Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs. Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet. We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade. Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke. The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied. However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between. Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively. Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays.

[Congenital lobar hyperinflation: conservative management as an alternative therapy]. / Hiperinsuflación lobar congénita: manejo conservador como alternativa terapéutica.

Congenital lobar emphysema used to be treated surgically. Congenital lobar hyperinflation is the currently recommended term, as it involves pathologically healthy lung tissue, which is why conservative management may be an option. Four cases of diagnosed congenital lobar hyperinflation are presented in which conservative treatment was chosen due to their clinical stability. Their outcome has been satisfactory with progressively normal radiology.

Clinical case: Combined pulmonary fibrosis and emphysema with pulmonary hypertension--clinical management.

BACKGROUND: Combined idiopathic pulmonary fibrosis (IPF) with pulmonary emphysema (CPFE) is a syndrome with a characteristic presentation of upper lobe emphysema and lower lobe fibrosis. While CPFE is a strong determinant of secondary precapillary pulmonary hypertension (PH), there is limited evidence regarding the management of patients with CPFE and PH. CASE PRESENTATION: A 63 year-old male presented in 2006 with dyspnoea on exertion having quit smoking in 2003. Clinical examination, together with high resolution computed tomography, bronchoalveolar lavage, and echocardiographic assessments, suggested a diagnosis of CPFE without PH. In 2007, the patient received intravenous cyclophosphamide, N-acetylcysteine, and short-term anticoagulation treatment. Due to remission of acute exacerbations, the patient received triple combination therapy (prednisone, N-acetylcysteine and azathioprine). Upon progressive clinical worsening, long-term supplemental oxygen therapy was initiated in 2009. Repeated right heart catheterisation in 2011 confirmed PH and worsening pulmonary haemodynamics, and off-label ambrisentan therapy was initiated. Dyspnoea remained at follow-up, although significant haemodynamic improvement was observed. CONCLUSION: CFPE is a distinct but under-recognized and common syndrome with a characteristic presentation. Further studies are needed to ascertain the etiology, morbidity, and mortality of CPEF with or without PH, and to evaluate novel management options.

Treatment of severe advanced emphysema with volume reduction using lung sealant: a case report of 2 patients.

BACKGROUND: Emphysema is a progressive and irreversible disease for which there is no cure to date. The patients experience debilitating shortness of breath with repetitive exacerbations and poor quality of daily life. At present, patients with severe emphysema have limited treatment options. Endoscopic lung-volume reduction with valve implantation or using lung sealant is a treatment option for patients with severe emphysema. By our patients, we detected collateral channels, which allow airflow into the target lobe and prevent atelectasis and significant lung-volume reduction. Thus, we decided to treat the advanced emphysema of our patients with endoscopic volume reduction using lung sealant (AeriSeal). Lung-volume reduction surgery reduces hyperinflation and improves lung function by removal of emphysematous lung tissue. However, lung-volume reduction surgery is also associated with significant short-term morbidity and mortality. Results from recently published Endobronchial Valve for Emphysema Palliation Trail (VENT) and Exhale Airway Stents for Emphysema (EASE) trial showed that treatment was substantially less effective and did not consistently reduce hyperinflation or improve lung function mostly likely due to collateral ventilation present in majority of patients. There is a volume reduction therapy in case of detection of collateral flow; use of a lung sealant is a possible alternative. METHODS: A novel endoscopic tissue sealant (AeriSeal; Aeris Therapeutics, Woburn, MA) is a liquid foam sealant that collapses hyperinflated lung areas destroyed by emphysema. The foam of lung sealant AeriSeal is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue, forming a film of material on the lung surface that seals the target region to cause durable absorption atelectasis. RESULTS: Two patients with advanced emphysema and hyperinflation underwent endoscopic volume reduction with endoscopic tissue sealant (AeriSeal); collateral flow was confirmed by using the Chartis System. Both patients experienced transient fever, malaise, chest discomfort, and shortness of breath for about 3 days after the procedure. Over a period of 8 and 12 weeks, the air within the sealed region was absorbed and the treated area showed atelectasis on computed tomography scan. The follow-up evaluations of those 2 patients showed improved lung function (increased FEV1, and a reduction of TLC and RV) with improved quality of life of both patients. CONCLUSIONS: Correlation and comparisons between changes in primary and secondary outcome measures in the lung function parameters and 6-minute walking test before and after the application of AeriSealant revealed significant reduction of hyperinflation and improvement both in the flow rates and physical capacity of our patients.

[Rectal ozone therapy for patients with pulmonary emphysema]. / La ozonoterapia en pacientes con enfisema pulmonar.

BACKGROUND: Ozone therapy may stimulate antioxidant systems and protect against free radicals. It has not been used formerly in patients with pulmonary emphysema. AIM: To assess the effects of rectal ozone therapy in patients with pulmonary emphysema. MATERIAL AND METHODS: Sixty four patients with pulmonary emphysema, aged between 40 and 69 years, were randomly assigned to receive rectal ozone in 20 daily sessions, rectal medicinal oxygen or no treatment. Treatments were repeated three months later in the first two groups. At baseline and at the end of the study, spirometry and a clinical assessment were performed. RESULTS: fifty patients completed the protocol, 20 receiving ozone therapy, 20 receiving rectal oxygen and 10 not receiving any therapy. At baseline, patients on ozone therapy had significantly lower values of forced expiratory volume in the first second (fEV1) and fEV1/forced vital capacity. At the end of the treatment period, these parameters were similar in the three treatment groups, therefore they only improved significantly in the group on ozone therapy. No differences were observed in other spirometric parameters. CONCLUSIONS: Rectal ozone therapy may be useful in patients with pulmonary emphysema.

La ozonoterapia en pacientes con enfisema pulmonar / Rectal ozone therapy for patients with pulmonary emphysema

Background: Ozone therapy may stimulate antioxidant systems and protect against free radicals. It has not been used formerly in patients with pulmonary emphysema. Aim: To assess the effects of rectal ozone therapy in patients with pul-monary emphysema. Material and Methods: Sixty four patients with pulmonary emphysema, aged between 40 and 69 years, were randomly assigned to receive rectal ozone in 20 daily sessions, rectal medicinal oxygen or no treatment. Treatments were repeated three months later in the frst two groups. At baseline and at the end of the study, spirometry and a clinical assessment were performed. Results: fifty patients completed the protocol, 20 receiving ozone therapy, 20 receiving rectal oxygen and 10 not receiving any therapy. At baseline, patients on ozone therapy had significantly lower values of forced expiratory volume in the frst second (fEV1) and fEV1/forced vital capacity. At the end of the treatment period, these parameters were similar in the three treatment groups, therefore they only improved significantly in the group on ozone therapy. No differences were observed in other spirometric parameters. Conclusions: Rectal ozone therapy may be useful in patients with pulmonary emphysema.

Biologic lung volume reduction therapy for advanced homogeneous emphysema.

This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

Intrabullous blood injection for lung volume reduction.

Bronchoscopic treatment for emphysematous lung diseases has attracted clinical attention, and several different approaches are being investigated. We present a case of emphysematous bullae that was effectively treated with a newly developed bronchoscopic intervention, autologous blood injection. A 59-year-old man was referred to our institution with exertional dyspnoea. Chest CT showed emphysema and bullae with a diameter of 12 cm in the right upper lobe. Bronchoscopic treatment was introduced as an alternative to surgery. Autologous blood and fibrinogen solution were infused into bullae via the transbronchial catheter, under fluoroscopic guidance. Post-treatment CT showed marked contraction of bullae to a diameter of 3 cm, corresponding to a volume reduction of 800 ml on body plethysmography. A significant reduction in dyspnoea was also noted. This therapeutic approach is less invasive and may represent a good option for reducing lung volume.

AANA journal course. Update for nurse anesthetists--part 4--life in the balance: the role of serpins in disease genesis and prevention.

Complex biological systems are often shaped and maintained by opposing forces. A relevant biological example is the delicate balance between proteases and their inhibitors. Serine proteases contain a serine residue in the active site of the molecule that is essential to the activity of the enzyme. Protease inhibitors limit the activity of proteases in the body. As examples, aprotinin (Trasylol), a serine protease inhibitor, and aminocaproic acid (Amicar), a lysine protease inhibitor, are used to decrease the rate of fibrinolysis and have recently been the subject of considerable controversy in the literature regarding safety and efficacy. This AANA journal course reviews 2 common examples of protease inhibitor disorders, angioedema and a form of emphysema, that are of particular anesthetic relevance.

Autologous transplantation of adipose tissue-derived stromal cells ameliorates pulmonary emphysema.

Adipose tissue is a useful tool for management of most complex cardiothoracic problems, including the reinforcement of damaged lungs, and adipose tissue-derived stromal cells (ASCs) have been suggested to secrete hepatocyte growth factor (HGF), a multipotent regenerative factor that contributes to the repair process after lung injury. The goal of this study was to demonstrate the therapeutic impact of autologous transplantation of ASCs through HGF supplementation for the enhancement of alveolar repair in a rat model of emphysema. ASCs were isolated from inguinal subcutaneous fat pads and characterized by flow cytometry. Cultured ASC were found to secrete significantly larger amounts of HGF (15 112 +/- 1628 pg per 10(6) cells) than other angiogenic factors. Transplantation of ASCs into elastase-treated emphysema models induced a significant increase in endogenous HGF expression in lung tissues with a small amount of increase in other organs, with the high levels lasting for up to 4 weeks after transplantation. Further, alveolar and vascular regeneration were significantly enhanced via inhibition of alveolar cell apoptosis, enhancement of epithelial cell proliferation and promotion of angiogenesis in pulmonary vasculature, leading to restoration of pulmonary function affected by emphysema. These data suggest that autologous ASC cell therapy may have a therapeutic potential for pulmonary emphysema, through inducing HGF expression selectively in injured lung tissues.

The singer's breath: implications for treatment of persons with emphysema.

This study investigated the effects of group singing instruction on the physical health and general wellness of senior citizens with emphysema. Subjects (n = 7) participated in 6 weeks of group vocal instruction, which emphasized breath management techniques. Dependent measures reflected physical health, functional outcomes, and quality of life. No significant differences were found on measures of physical health (FEV1, inspiratory threshold, distance walked, and The DUKE physical health subscale). Measures of functional outcomes each showed a significant change across time. Results of the ANOVAs for breath management (extent of counting) and breath support (intensity of speech) were significant (p < .038 & p < .000 respectively). Descriptive analyses showed a clear and dramatic shift in breathing mode from clavicular to diaphragmatic breathing that was maintained 2 weeks after the treatment period. Quality of life measures (subjective scales and The Duke Health Profile) yielded mixed results. Findings of this study suggest that vocal instruction, inclusive of breathing exercises, may help to improve the quality of life for senior citizens with emphysema. Subjects in this study responded positively to the instruction and further investigation of the treatment method is warranted.

[The effects of incentive spirometry on pulmonary functions].

The effects of incentive spirometry on pulmonary functions were studied in 46 normal adults of advanced age ('N' group) and 42 patients with chronic pulmonary emphysema ('E' group). Subjects of the both groups carried out deep breathing exercises by using incentive spirometry, 'Souffle', for five minutes, five times daily for four weeks. Pulmonary functions and arterial blood gases were measured at the start of exercise program, and at two and four weeks after the start. Both groups showed significant increases in VC, FEV1.0, peak expiratory flow, the flow at 75 percent VC (V75), maximal voluntary ventilation and PaO2, and a significant decrease in A-aDO2 at both two and four weeks after the start. In addition, V25 increased significantly in 'E' group. It is concluded that 'Souffle' is one of the useful preoperative respiratory managements for elderly patients and those with chronic pulmonary emphysema.

Pneumotórax iatrogênico por acupuntura / Iatrogenic pneumothorax due to acupunture

Um paciente com 68 anos de idade, branco e com diagnóstico prévio de enfisema pulmonar, foi tratado com acupuntura. As agulhas foram inseridas na regiäo precordial e imediatamente após o paciente apresentou piora da dispnéia. Quatro dias após, pneumotórax esquerdo foi visto na radiografia de tórax. Houve expansäo total do pulmäo após drenagem torácica

[Iatrogenic pneumothorax caused by acupuncture]. / Pneumotórax iatrogênico por acunputura.

A 68 year-old white male patient with previous diagnosis of pulmonary emphysema was submitted to acupuncture. The needles were inserted into the precordial area and the patient immediately complained of worsening dyspnea. Four days later pneumothorax was detected by chest X-rays. A thoracic tube was inserted with total lung expansion.