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Lung volume reduction surgery has proven benefits in emphysema. However, high postoperative morbidity and stringent selection criteria for suitable candidates are limitations in clinical practice. Endoscopic approaches to lung volume reduction have used a range of different techniques such as endobronchial blockers, airway bypass, endobronchial valves, biologic sealants, and airway implants to address the limitations of surgery. The underlying physiologic mechanisms of endoscopic modalities vary, and homogeneous and heterogeneous emphysema are targeted. Currently available data on efficacy of bronchoscopic lung volume reduction are not consistently conclusive, and subjective benefit in dyspnea scores is a more frequent finding than improvements on spirometry or exercise tolerance. The safety data are more promising, with rare procedure-related mortality, fewer complications than lung volume reduction surgery, and short hospital length of stay. The field of bronchoscopic lung volume reduction continues to evolve as ongoing prospective randomized trials aim to clarify the efficacy data from earlier feasibility and safety studies., (Copyright 2010. Published by Elsevier Inc.)

Congenital lobar emphysema (CLE) is a rare congenital abnormality characterised by overinflation of a pulmonary lobe. Its aetiology is unknown. The management of CLE has traditionally been surgical. A newborn boy with a birthweight of 2.5 kg was delivered at full-term by caesarian section due to food delivery. There was no marked respiratory distress at birth, and little meconium stained liquor was seen on the skin. The initial diagnosis was meconium aspiration syndrome. After computed tomography of the thorax, CLE was diagnosed. The patient was observed throughout for a week and the CT of the thorax was repeated, which revealed that the emphysema had resolved. The nonoperative approach should be considered in asymptomatic patients with CLE.

Case Report: A middle-aged man presented with the diagnosis of typical spontaneous pneumothorax in the left chest. His management was initiated as usual with a chest drain and he had an uneventful recovery with good expansion of the affected lung up until the third postoperative day. But due to a fatal accident, the patient connected the oxygene supply tube into his thoracic drain. This high pressure caused a left, and a consequent bilateral pneumothorax with massive subcutanous emphysema, being the cause of a preterminal status. Cardio-pulmonary resuscitation was unsuccesfull and the patient died. Intentional suicide was excluded by forensic investigations., Discussion: According to our knowledge, no similar case with this mechanism of tension pnemuthorax has been published in the literature so far. The pathophysiology is similar to lung damage due to high-pressure ventillation with consecutive tension pneumothorax.

Phage display of random peptide libraries is a powerful, unbiased method frequently used to discover ligands for virtually any protein of interest and to reveal functional protein-protein interaction partners. Moreover, in vivo phage display permits selection of peptides that bind specifically to different vascular beds without any previous knowledge pertaining to the nature of their corresponding receptors. Vascular targeting exploits molecular differences inherent in blood vessels within given organs and tissues, as well as diversity between normal and angiogenic blood vessels. Over the years, our group has identified phage capable of homing to lung blood vessels based on screenings using immortalized lung endothelial cells combined with in vivo selections after intravenous administration of combinatorial libraries. Peptides targeting lung vasculature have been extensively characterized and a lead homing peptide has shown interesting biological properties, bringing novel insights as to the implications of lung endothelial cell apoptosis in the pathogenesis of emphysema. We have also designed and developed targeted nanoparticles with imaging capabilities and/or drug delivery functions by combining phage display technology and elemental gold (Au) nanoparticles, constituting a promising platform for the development of therapeutic agents for imaging and treatment of lung disorders. Given the important role of the endothelium in the pathogenesis and progression of several diseases associated with the airways, ligand-directed discovery of lung vascular markers is an important milestone toward the development of future targeted therapies.

Background: For decades, the well-established standard recommended treatment for patients with congenital lobar emphysema (CLE) and respiratory distress has been lobectomy of the affected lobe or lobes, whereas indications for conservative management have been controversially discussed., Patients/methods: Description of the clinical courses including the results of diagnostic procedures and the resulting therapeutic strategies in 2 patients with congenital lobar emphysema. We review the literature on conservatively treated patients with congenital lobar emphysema., Results: Considering that formerly asserted hypotheses postulating benefits of surgical treatment cannot unambiguously be corroborated from cases in literature, we could show that conservative treatment in patients with congenital lobar emphysema is appropriate in mildly to moderately symptomatic children., Conclusion: Conservative treatment of children with congenital lobar emphysema is an attractive option, whenever justifiable on medical grounds. Our cases may serve as paradigms in decision-making processes in similar cases and - together with the literature review - may be helpful to avoid unnecessary lobectomies in children. Patients treated conservatively will need a close follow-up, and further data on long-term follow-up courses are desirable.

Emerging treatments require appropriate CT targeting of a selected lobe or lobes and target airways to obtain a successful response. CT scan is used in pretreatment planning to select patients and plan treatment strategy and posttreatment to confirm correct deployment of devices and assess treatment response. Increasingly treatments are being developed to treat patients who have emphysema who require accurate quantitation of extent and distribution of the process. Functional assessment can be made by inference of detailed anatomic correlates and by direct measurement of regional function using dynamic scan protocols. This article summarizes the current role of imaging in the assessment of patients who have emphysema.

Surgery for severe emphysema involves a cohort of patients who are already at risk for increased perioperative morbidity and mortality. Through the careful screening and selection process, improved intraoperative techniques and rigorous attention to postoperative care, the NETT managed to yield acceptable improvements in survival and functional outcomes in this fragile patient cohort and these benefits were sustained over the long-term. Identification of the characteristics associated with a higher risk of death has provided tangible patient selection criteria for the ongoing application of LVRS. Because the NETT was such a large-scale study, the protocols that were developed had to be standardized across several centers. This produced reliable and reproducible standards for evaluation and treatment that can be applied to the surgical treatment of emphysema. When considering these criteria, although individualized patient selection is important, only patients with upper-lobe predominant disease on chest CT and possibly those with non-upper-lobe predominant disease who also have low baseline exercise capacity are appropriate candidates for LVRS. Expectedly, questions remain regarding the exact mechanism whereby the benefits derived from LVRS are obtained. Additionally, the benefit of LVRS in patients with heterogeneous but non-upper-lobe predominant disease remains to be further elucidated. In spite of the limitations of the study, the NETT, through a tremendous coordinated effort, provided valuable outcomes data, answered the pressing questions regarding lung volume reduc-tion surgery that existed at the time, and provided valuable insight into other facets of emphysema physiology and management through direct observation. Based on the NETT findings, in November 2003, CMS published criteria for expanded coverage for LVRS to include non-high-risk patients who demonstrated either upper-lobe predominant emphysema, or non-upper-lobe predominant emphysema and low baseline exercise capacity and who met the screening guidelines.29 This study not only provided data regarding the clinical efficacy of LRVS, but it was instrumental in determining health policy guidelines for the surgical management of emphysema.

Rationale: Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling., Objectives: Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema., Methods: Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life., Measurements and Main Results: After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4 +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life., Conclusions: BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

Physical activity is an important parameter related to morbidity and mortality in cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer, and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of physical activity as reported by the patients are associated with a faster annual lung function decline, increased number of hospitalizations, and higher risk of mortality. Self-reported physical activity, however, correlates only poorly with objectively quantified physical activity in patients with COPD. Recent data show that physical activity can reliably be measured in a substantial number of patients with COPD. Extrapulmonary effects of COPD are associated with reduced physical activity. Clinical characteristics commonly used to assess disease severity like the forced expiratory volume in 1 s or the 6-min walk distance only incompletely reflect the physical activity of patients with COPD.

Endobronchial lung volume reduction (ELVR) may be helpful in a selected group of patients with advanced stages of emphysema. However, collateral ventilation (CV) from adjacent lobes through collateral channels often prevents target lobe atelectasis, which presumably mediates clinical responses after ELVR. With the goal of identifying patients who are more or less likely to benefit, we propose endobronchial CV assessment (ECVA), a novel catheter-based endobronchial approach, to quantitatively determine the resistance of collateral channels (R(coll)). ECVA relies on the measurement of spontaneous airflow from the sealed and isolated target compartment during spontaneous respiration in an awake subject, thereby providing a direct, simple, and minimally invasive method of assessing R(coll) in lungs. In this study, we validated ECVA in a controlled laboratory setup and tested ECVA's clinical feasibility in 11 emphysematous human subjects undergoing ELVR treatment. To evaluate ECVA in a controlled laboratory setup with known CV levels, we built a benchtop model mimicking a simple one-compartment model of the lungs during temporary compartmental occlusion and spontaneous respiration, which could be adapted to hold restrictors of different sizes representing collateral airways, and applied ECVA to estimate the resistance of various benchtop model restrictors. We then rated ECVA's performance by direct comparison between estimated and actual restrictor resistance and found a correlation coefficient near one. To test ECVA's clinical performance, post-ELVR radiological assessments were made to determine the occurrence of atelectasis in the treated lobe, and interlobar R(coll) was estimated in the target lobe via ECVA pre-ELVR. ECVA could be completed in all patients with no adverse events, and a high R(coll) by ECVA predicted absorption atelectasis following ELVR ( P = 0.005). We believe that ECVA may be helpful to distinguish those patients with and without interlobar CV by identifying the critical value of R(coll) above which atelectasis is likely to occur.

Purpose of Review: Interventional pulmonology is a rapidly expanding field offering less invasive therapeutic procedures for significant pulmonary problems. Many of the therapies may be new for the anesthesiologist. Although less invasive than surgery, some of these procedures will carry significant risks and complications. The team approach by anesthesiologist and pulmonologist is key to the success of these procedures., Recent Findings: Many modalities for central airway obstruction have emerged, including the expanding application of airway stenting procedures. Diagnostic bronchoscopy with ultrasound guidance promises great advances in lung cancer staging. New bronchoscopic treatments of asthma and emphysema are actively under investigation. Advances in anesthetic agents and techniques for interventional pulmonology procedures have also occurred., Summary: This review is intended to familiarize the anesthesiologist with current and rising therapeutic modalities for pulmonary disease. Knowledge of interventional pulmonology facilitates planning and preparation for well tolerated and effective procedures.

Combined pulmonary fibrosis and emphysema (CPFE) is a frequently under-diagnosed condition. Isolated pulmonary function tests (PFT) can give rise to misinterpretations. We have found no reports on these patients' spirometric progression. We describe two cases of CPFE, showing long-term functional evolution to have a more accurate understanding of current spirometric values. The most relevant findings are: 1) spirometry with discrete functional alterations in the presence of a marked dyspnea and the need, in one patient, for chronic oxygen therapy; and 2) functional evolution reflecting "pseudonormalisation" of the initial obstructive spirometric pattern, possibly as a result of fibrosis development. A mild obstructive defect in a patient with chronic airflow limitation and marked impairment of his/her clinical status and functional class should alert on the possibility of associated pulmonary fibrosis. A computed tomography (CT) and previous PFTs will allow a better understanding of this condition.

We describe the case of a 61-year-old male patient, in which the search for the cause of chronic respiratory failure, severe pulmonary hypertension and secondary erythrocytosis resulted in a diagnosis of combined pulmonary fibrosis and emphysema (CPFE). This is a unique, recently characterised syndrome with upper-lobe emphysema and pulmonary fibrosis of the lower lungs. The cause is unknown, but one of the main risk factor remains smoking. The patient was a heavy smoker (over 40 pack-years). He complained of dyspnoea on exertion and cough. Physical examination revealed basal crackles and cyanosis. The patient had severe reduction in diffusing capacity, out of proportion to his lung volumes (DLCO 27% of predicted value, FEV1 2.95 l (100%), FVC 4.41 l (118%), FEV1/FVC (66%). The blood gas showed hypoxemia (pO2 37 mm Hg), hypocapnia and respiratory alkalosis. Diagnosis was based on chest computer tomography, which revealed upper lobe emphysema and lower lobe ground glass changes and honeycombing. Severe pulmonary hypertension (SPAP 80 mm Hg) was confirmed by echocardiography and right cardiac catherisation. The patient received long-term oxygen therapy, inhaled corticosteroid and Ca-blocker.

The aim of the present study was to correlate clinical outcome measures following treatment with bronchial valves with regional lung volume. Computed tomography (CT) scan data from 57 subjects with severe emphysema were obtained from nine North American clinical trial sites. IBV(R) Valves (Spiration, Inc., Redmond, WA, USA) were placed to occlude segmental and subsegmental bronchi in right and left upper lobes using a flexible bronchoscope. Subjects completed a St George's Respiratory Questionnaire (SGRQ), pulmonary function test (PFT) and exercise capacity test. CT scans were analysed at baseline and at 1, 3 or 6 months after treatment to measure total and lobar lung density, volume and mass. Total lung volumes measured using CT were strongly correlated with PFT and did not change with treatment. However, the treated upper lobes significantly decreased in volume in 88% of the observations, by mean+/-sd 335+/-444 mL, or a decrease of 10.2% in the 6 month data. The untreated lobes had an 11.6% increase in volume. Changes in regional lung volume were associated with clinically meaningful improvements in SGRQ (-8.95+/-16.22), but not clinically meaningful PFT changes. The significant health status improvements reported by subjects following bilateral bronchial valve treatment are associated with regional lung volume changes and interlobar shift measured using computed tomography.

We describe the combined use of inhaled nitric oxide and heliox (79% helium and 21% oxygen) as a rescue therapy for a critically ill infant with localized interstitial pulmonary emphysema and pulmonary hypertension. Conventional interventions were ineffective, not feasible, or unlikely to take effect in time, during this infant's acute critical illness. We added heliox based on its known pulmonary effects, and inhaled nitric oxide to improve oxygenation, after echocardiographic evidence of high right-ventricular pressure. The infant made a full recovery. To our knowledge this is the first case report of heliox and inhaled nitric oxide used simultaneously in localized interstitial pulmonary emphysema.

Background: Nearly 50 years ago, Wilson and Mikity described a syndrome (WMS) of chronic lung disease (CLD) in premature infants, characterized by early development of cystic interstitial emphysema (PIE), despite minimal ventilatory support. The validity of the diagnosis is currently unclear; now considered either an anachronism, part of BPD spectrum or included within various poorly defined diagnoses such as chronic pulmonary insufficiency of prematurity (CPIP)., Objectives: To define clinically useful diagnostic criteria for WMS so its position in the spectrum of CLD of infancy can be established., Methods: We studied nine patients who fulfilled WMS criteria, combining this data with a detailed review of the available literature., Results: Despite minimal respiratory support at birth, all developed generalized or lobar cystic PIE by 3 weeks of age, followed by slow inflammatory progression over a further 2-3 months. Final outcome was variable but most were left with some degree of CLD., Conclusions: WMS is a rare but clearly identifiable syndrome with significant morbidity, predominantly affecting infants below 1,500 g birth weight. The earliest pathology appears to be alveolar air leak. Inflammatory activation induced by cystic interstitial air may cause the subsequent progressive respiratory disease. Management is supportive but should include investigation for pulmonary hypertension., ((c) 2008 Wiley-Liss, Inc.)

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients., Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival., Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components., Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components., Conclusions: The mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Persistent pulmonary interstitial emphysema is a chronic disease reported in mechanically ventilated premature newborns. We describe a case of localized persistent pulmonary interstitial emphysema in a preterm infant without mechanical ventilation but on continuous positive airway pressure using nasal prongs. The condition resolved without surgery.

Background: Continuous oxygen therapy is not recommended for emphysema patients who are not hypoxemic at rest, although it is often prescribed. Little is known regarding the clinical characteristics and survival of nonhypoxemic emphysema patients using continuous oxygen. Analysis of data from the National Emphysema Treatment Trial (NETT) offers insight into this population., Methods: We analyzed demographic and clinical characteristics of 1,215 participants of NETT, stratifying by resting PaO(2) and reported oxygen use. Eight-year survival was evaluated in individuals randomized to medical therapy., Results: At enrollment, 33.8% (n = 260) of participants nonhypoxemic at rest reported continuous oxygen use. When compared to nonhypoxemic individuals not using oxygen (n = 226), those using continuous oxygen had worse dyspnea, lower quality of life, more frequent exercise desaturation, and higher case-fatality rate. After adjusting for age, body mass index, and FEV(1) percentage of predicted, the presence of exercise desaturation accounted for the differential mortality seen between these groups., Conclusions: In the NETT, the use of continuous oxygen in resting nonhypoxemic emphysema patients was associated with worse disease severity and survival. The differential survival observed could nearly all be accounted for by the higher prevalence of exercise desaturation in those using continuous oxygen, suggesting that it is not a harmful effect of oxygen therapy contributing to mortality. It remains unclear whether continuous oxygen therapy improves survival in normoxic patients with exercise desaturation.

Pneumopericardium is the least common form of air leak in infants. A tension pneumopericardium is even more infrequent but associated with a very high mortality rate. We describe the case of an unsuccessful resuscitation in a preterm infant due to a pneumothorax and tension pneumopericardium. Despite relatively mild pressure ventilation the patient developed massive pulmonary interstitial emphysema. The extra-alveolar air spread from the interstitium towards the mediastinal space (Macklin effect) and caused a pneumothorax and pneumopericardium, which evolved towards a tension pneumopericardium after a traumatic mechanical procedure. The infant deteriorated acutely. Despite prompt pleural drainage there were no signs of recovery at any time. Postmortal examination revealed a tension pneumopericardium and massive interstitial pulmonary emphysema, which was not obvious on radiographical investigation. In cases of acute deterioration of a ventilated neonate, one should always rule out pneumothorax. If the patient does not recover after pleural drainage and cardiac resuscitation a (tension) pneumopericardium should be considered.

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally grave.

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.

Computed tomographic based indices of emphysematous lung destruction may highlight differences in disease pathogenesis and further enable the classification of subjects with Chronic Obstructive Pulmonary Disease. While there are multiple techniques that can be utilized for such radiographic analysis, there is very little published information comparing the performance of these methods in a clinical case series. Our objective was to examine several quantitative and semi-quantitative methods for the assessment of the burden of emphysema apparent on computed tomographic scans and compare their ability to predict lung mechanics and function. Automated densitometric analysis was performed on 1094 computed tomographic scans collected upon enrollment into the National Emphysema Treatment Trial. Trained radiologists performed an additional visual grading of emphysema on high resolution CT scans. Full pulmonary function test results were available for correlation, with a subset of subjects having additional measurements of lung static recoil. There was a wide range of emphysematous lung destruction apparent on the CT scans and univariate correlations to measures of lung function were of modest strength. No single method of CT scan analysis clearly outperformed the rest of the group. Quantification of the burden of emphysematous lung destruction apparent on CT scan is a weak predictor of lung function and mechanics in severe COPD with no uniformly superior method found to perform this analysis. The CT based quantification of emphysema may augment pulmonary function testing in the characterization of COPD by providing complementary phenotypic information.

Patients with emphysema may experience reduced health-related quality of life (HRQOL). HRQOL measures have evolved from two different measurement traditions: psychometric theory and decision theory. Psychometric methods typically create a profile of outcomes, whereas decision theory methods offer a summary score on a continuum ranging from 0.0 (for death or worst possible health) to 1.0 (for best possible health). Decision theory methods are better suited for cost-effectiveness studies. Generic HRQOL measures can be applied to any disease population, whereas disease-targeted measures are tailored to a specific clinical condition. Disease-targeted measures are typically more sensitive to clinical change, but cannot offer a comparison basis for different clinical conditions. This article reviews the measurement of HRQOL in patients with emphysema. The National Emphysema Treatment Trial (NETT) offers an example of the application of both generic and disease-targeted, as well as profile and decision theory, methods. The NETT illustrates how HRQOL measures can be used to assess outcomes and estimate cost-effectiveness in a major clinical trial.

Background and Objective: Hyperinflation with a decrease in inspiratory capacity (IC) is a common presentation for both unstable and stable COPD patients. As CPAP can reduce inspiratory load, possibly secondary to a reduction in hyperinflation, this study examined whether CPAP would increase IC in stable COPD patients., Methods: Twenty-one stable COPD patients (nine emphysema, 12 chronic bronchitis) received a trial of CPAP for 5 min at 4, 7 and 11 cmH(2)O. Fast and slow VC (SVC) were measured before and after each CPAP trial. In patients in whom all three CPAP levels resulted in a decreased IC, an additional trial of CPAP at 2 cmH(2)O was conducted. For each patient, a 'best CPAP' level was defined as the one associated with the greatest IC. This pressure was then applied for an additional 10 min followed by spirometry., Results: Following application of the 'best CPAP', the IC and SVC increased in 15 patients (nine emphysema, six chronic bronchitis). The mean change in IC was 159 mL (95% CI: 80-237 mL) and the mean change in SVC was 240 mL (95% CI: 97-386 mL). Among these patients, those with emphysema demonstrated a mean increase in IC of 216 mL (95% CI: 94-337 mL). Six patients (all with chronic bronchitis) did not demonstrate any improvement in IC., Conclusions: The best individualized CPAP can increase inspiratory capacity in patients with stable COPD, especially in those with emphysema.

Various psychological and cognitive difficulties have been documented in patients with emphysema. The aim of this article is to review prior literature on the prevalence of these difficulties in emphysema, as well as identify specific studies demonstrating improvement in these areas after therapy. Traditional therapies such as continuous and intermittent oxygen therapy and comprehensive pulmonary rehabilitation are reviewed. In general, these studies demonstrate reductions in symptoms of depression and anxiety as well as specific improvements in complex attention and verbal fluency. In a more recent study, patients with emphysema who underwent lung volume reduction surgery (LVRS) demonstrated improved psychomotor speed, verbal memory, and naming skills at 6 months compared with patients with emphysema who were in comprehensive rehabilitation only. The patients with emphysema who had LVRS also demonstrated greater decline in depressive symptoms compared with the rehabilitation patients at 6 months. There were no associations between improved neuropsychological tests and changes in depression, exercise tests, pulmonary function, oxygenation, or quality of life scores, and thus the mechanism of behavioral improvement identified in the patients who underwent LVRS remained unclear. Overall, studies suggest that psychological and cognitive improvements occur subsequent to a variety of medical and behavioral treatment therapeutic approaches, and that LVRS appears to have an advantage for some patients with emphysema.

Background/rationale: Expected value of information (EVI) analyses allow researchers to estimate the returns to conducting research. We used EVI techniques to estimate the value of the National Emphysema Treatment Trial (NETT), a multicenter randomized trial of lung-volume-reduction surgery (LVRS) versus medical therapy (MT) for patients with severe emphysema, then compared that result to the trial cost., Methods: We gathered information on costs and benefits of LVRS and MT before the trial and the costs of conducting the NETT, and compared these data with the results of the cost-effectiveness analysis conducted alongside the trial. We used 2 thresholds to represent the societal value of a quality-adjusted life year (QALY): USD 50,000 and USD100,000., Results: The cost effectiveness of LVRS versus MT using historical (nontrial) information was USD 305,000/QALY. Based on these data and the threshold incremental cost-effectiveness ratio values, the expected value of perfect information was USD 46 million and USD 670 million for thresholds USD 50,000 and USD 100,000 per QALY, respectively. The NETT was powered for 1,250 patients in each arm; ultimately approximately 600 patients in each arm were recruited. With 1,250 patients per arm, the expected value of sample information was USD 660 million for the threshold of USD100,000. The actual cost of the NETT was approximately USD 60 million. The expected net benefit of sampling was USD 600 million., Conclusions: Given the difference between the cost of the trial and the economic benefits of the information, the EVI analyses suggest that federal investment in the NETT trial represented good value for money.

COPD is a frequent disease, affecting approximately one in four smokers. In older patients > 70 years of age, the proportion of individuals who never have smoked increases up to one in three individuals. Severe disease is present in 10%, and the limitation of performance is usually caused by airway obstruction, in a smaller portion of patients by the loss of alveolar surface (emphysema). After medical treatment with antiobstructive and anti-inflammatory drugs, oxygen remains a major therapy option. With it, hypercapnic patients benefit most from long-term therapy. Patients with predominant emphysema benefit most from high-flow (6-8 l/min) oxygen therapy during exercise. Permanent yellow or greenish sputum decoloration is suggestive of chronic bacterial colonization. This group of patients may benefit from a permanent inhalative therapy with antibiotics (mainly aminoglycosides). There is growing evidence from current literature to support this concept. If dyspnea is severe, especially during mild exercise, a subset of patients might benefit from the use of long-acting morphium. Goal of this therapy is to downregulate breathing control. Predominantly "pink puffers" seem to respond. A dose of 10-20 mg will usually be sufficient. Life-threatening hypercapnia is usually not observed with this form of therapy. Noninvasive ventilation is an option for patients with severe hypercapnia. Thereby, ventilatory pressure or inspiratory volume should be selected to effectively unload the respiratory muscles. This will increase quality of life. Life span is likely to be prolonged, however, comparative data where patients were effectively ventilated (as seen on the reduction of hypercapnia) are missing. A multicenter trial addressing this topic is currently being conducted in Germany. Independent of the severity of COPD, patients in general benefit from physical training with alternation of endurance and interval training being most effective. This will decrease the number of hospital admissions and probably mortality as well. Lung volume reduction surgery virtually treats lung hyperinflation. Bullectomy is still considered effective for isolated bullous emphysema as well as lobectomy, if this portion of the lung is without function. Shaving procedures are still associated with high rates of complications and should only be performed in selected cases. Effectiveness of endoscopic lung volume reduction surgery by implantation of plugs or valves cannot be assessed yet. First data are rather disappointing. Ultimate alternative remains lung transplantation with life expectancy ranging between 5-6 years independent of age. Indeed, consequent application of previously described measures might preserve a stable state over many years.

Background: Unilateral giant pulmonary interstitial emphysema (PIE) can be seen as a complication of chronic ventilation in extremely low-birth-weight babies. Many can be managed by conventional pulmonary care which includes positioning, suctioning, chest physiotherapy, gentle conventional ventilation and high-frequency ventilation. Some may need invasive procedures such as lung puncture, pleurotomies and excisional surgery. This is the group in which single-lung ventilation may be beneficial and circumvent the need for an invasive procedure., Objective: We describe the technique of single-lung ventilation using a Swan-Ganz catheter to block the main stem bronchus on the diseased side in air-leak syndromes., Materials and Methods: A retrospective chart review was done on 17 newborns undergoing single-lung ventilation using this technique at the Children's Hospital of New York, Columbia University, from 1986 to 2000., Results: The technique was successful in the management of severe, neonatal unilateral lung disease not responsive to conventional modes of therapy in all but two neonates as seen by a significant improvement in pH and a decrease in PaCO(2) levels. In one neonate malpositioning of the Swan-Ganz catheter balloon could have contributed to the development of pneumothorax., Conclusion: The described technique of single-lung ventilation provides a safe, minimally invasive and economically feasible method of management of unilateral giant PIE in newborns not responsive to conventional modes of therapy with minimal complications.

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.

Computer-aided diagnosis (CAD) technology is becoming an important tool to assess treatment response in clinical trials. However, CAD software alone is not sufficient to conduct an imaging-based clinical trial. There are a number of architectural requirements such as image receive (from multiple field sites), a database for storing quantitative measures, and data mining and reporting capabilities. In this paper we describe the architectural requirements to incorporate CAD into clinical trials and illustrate their functionality in therapeutic trials for emphysema.

A syndrome including upper-lobe emphysema and pulmonary fibrosis of the lower lungs was recently characterized. It is found most often in men who are smokers or ex-smokers of more than 40 pack-years; their mean age is 65 years. Exertional dyspnea is always present. There are basal crackles. The disease has no known cause; the only certain risk factor is smoking. Pulmonary function tests show respiratory volumes and flows that are often normal or subnormal, while carbon monoxide transfer is substantially reduced and exercise hypoxemia is present. Diagnosis is based on findings from millimeter-slices of computed tomography of the chest, which show either centrilobular emphysema or upper-zone bullous emphysema, associated in 90% of cases with very suggestive paraseptal emphysema and diffuse infiltrating fibrosing lung disease at the bases (subpleural reticular opacities, honeycomb images, traction bronchiectasis), with more frequent ground glass opacities than in idiopathic pulmonary fibrosis. Pulmonary hypertension is present in almost half of all patients and represents the principal negative prognostic factor for this condition, which has a median survival of 6 years.

Hyperacute rejection is an early complication of transplantation, caused by the presence in the recipient of pre-formed donor-directed antibodies (Ab). We report a case of fatal early graft dysfunction after lung transplantation in a female recipient with no anti-HLA Ab detected before transplantation. Further immunologic studies revealed the presence, in the pre-transplant serum, of low-titer anti-HLA Ab directed against the donor's HLA, detectable only by flow-cytometry screening for panel-reactive antibodies. This observation emphasizes the importance of sensitive Ab detection in patients awaiting lung transplantation. Women should be specifically targeted for such sensitive Ab detection.

Bullae are common accompaniments of chronic obstructive pulmonary disease especially emphysema. They contribute to increased lung volume and worsen the mechanical disadvantage of the inspiratory muscles by increasing the residual volume (RV) and RV/total lung capacity ratio. Thus effective decompression of a large bulla or bullae is thus important to improve the lung function of affected patients and also to provide symptomatic relief. Surgery and thoracoscopy are two commonly performed procedures used to treat bullae. Although bronchoscopic lung volume reduction has been successfully accomplished for emphysema, isolated decompression of bullae bronchoscopically has not been tried to date. A large emphysematous bulla in the left lower lobe of a surgically unfit patient was bronchoscopically punctured with a transbronchial aspiration needle; the position of the needle inside the bulla was confirmed and the air from the bulla was aspirated slowly to allow collapse. Finally, some autologous blood was instilled into the bulla before the needle was withdrawn. The patient had immediate and sustained symptomatic relief with significant improvement in lung function. Bronchoscopic transbronchial decompression of emphysematous bullae can be an effective therapeutic option and warrants further investigation.

Using clinical and claims records from the National Emphysema Treatment Trial, we sought to identify factors that accurately predicted COPD exacerbations. This prospective cohort study consisted of subjects with severe emphysema randomized to medical therapy. Exacerbations were defined as a hospitalization or emergency department visit for COPD. Patient characteristics obtained before randomization were entered as independent variables in multivariable logistic regression models to estimate the risk of exacerbation. Discrimination was determined using the area under the receiver operator characteristic curve (AUC). Baseline measures included demographics, body mass index, pulmonary function, arterial blood gases, radiology studies, dyspnea (Shortness of Breath Questionnaire - SOBQ), health-related quality of life (St. George's Respiratory Questionnaire - SGRQ), 6-minute walk, exercise capacity, medication use, prior exacerbations and co-morbidity. In 610 participants, 26.6% had a COPD exacerbation over 1-year follow-up. In a model incorporating spirometry, PaO2, dyspnea, prior exacerbations and co-morbidity, a 5-point decrement in percent predicted FEV1 (OR 1.16, 95% CI 1.00-1.34) and a 5-point worsening in SOBQ (OR 1.08, 1.02-1.14) independently predicted exacerbations (AUC for full model 0.68). Combining physiologic variables, dyspnea, prior exacerbations and co-morbidity may be useful in identifying patients at high risk for COPD exacerbations.

Pulmonary interstitial emphysema (PIE) contributes to worsening respiratory status in already compromised premature infants. Various treatments for PIE include high-frequency ventilation, postural therapy, pneumonectomy or lobectomy and selective bronchial intubation. While right main stem bronchus intubation is easy to perform at the bedside for treatment of PIE in the left lung, left main stem bronchus intubation for the treatment of right-sided PIE remains challenging and the technique was rarely reported and poorly described. In this case report, we revisit this procedure and describe successful treatment of right lung PIE with hyperinflation by selective left main stem intubation at 2 weeks of life in a 24-week-old premature infant who had respiratory distress syndrome and pulmonary hemorrhage. A detailed description is given to allow clinical bedside replication following specific anatomic landmarks.

Objectives: Minimally invasive endoscopic treatment of emphysema could provide palliation with less risk than lung volume reduction surgery and offer therapy to patients currently not considered for lung volume reduction surgery. The Intrabronchial Valve is used to block bronchial airflow in the most emphysematous areas of lung., Methods: Patients with severe chronic obstructive pulmonary disease and heterogeneous upper lobe-predominant emphysema were eligible. Patients underwent flexible bronchoscopic placement of valves into segmental or subsegmental airways in both upper lobes. Outcomes assessed over a minimum of 6 months of follow-up included the safety, feasibility, tolerance, and success of valve placement; health-related quality of life; exercise capacity; pulmonary function; and gas exchange., Results: Five centers treated 30 patients. Patient follow-up ranged from 1 to 12 months. A mean of 6.1 valves were placed per patient. Valves were positioned by means of flexible bronchoscopy in 99% of desired airways, and the procedure duration ranged from 15 to 125 minutes (mean, 65 minutes). Hospital discharge occurred within 2 days in 27 of 30 patients. There were no deaths or episodes of valve migration, tissue erosion, or significant bleeding. Eighty-three percent of patients had no adverse events judged probably or definitely related to the device. Patients experienced significant improvement in health-related quality of life, although the physiologic and exercise outcomes did not show statistically significant improvements., Conclusions: These first multicenter results with the Intrabronchial Valve demonstrate significant improvements in health-related quality of life and acceptable safety, ease of use, and procedural complication rates. The valve might be a safer and less-invasive alternative to surgical therapy for patients with severe emphysema.

Emphysema is caused by exposure to cigarette smoking as well as alpha(1)-antitrypsin deficiency. It has been estimated to cost the National Health Service (NHS) in excess of 800 million pounds per year in related health care costs. The challenges for Critical Care nurses are those associated with dynamic hyperinflation, Auto-PEEP, malnutrition and the weaning from invasive and non-invasive mechanical ventilation. In this paper we consider the impact of the pathophysiology of emphysema, its effects on other body systems as well as the impact acute exacerbations have when patients are admitted to the Intensive Care Unit.

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.

Surgical bullectomy is the treatment of choice for giant emphysematous bulla. We report a case of successful nonsurgical treatment with bronchoscopic placement of one-way endobronchial valves that are currently under investigation for the treatment of end-stage emphysema. In patients who are poor surgical candidates, this noninvasive bronchoscopic treatment may represent a valuable alternative.

Background: Oxygen consumption volume (VO2) and resting energy expenditure are increased in emphysema because of impaired respiratory function and mechanics, with greater oxygen cost of breathing and altered metabolism. We hypothesized that lung volume reduction surgery may improve energy expenditure and metabolism., Methods: In this 1-year prospective study, 30 patients with moderate-to-severe emphysema underwent bilateral lung volume reduction surgery; 28 similar patients, who refused operation, followed a standard respiratory rehabilitation program. Oxygen consumption volume and resting energy expenditure, both corrected for fat-free mass, VO2 proportion of respiratory muscles (%VO2Resp), respiratory quotient, and energy substrate oxidation were determined by using a calorimetric chamber with indirect methods., Results: Only after surgery significant improvements resulted in 1-second forced expiratory volume (+20.4%, p = 0.009), residual volume (-24.8%, p = 0.001), diffusion-lung carbon-monoxide (+18.4%, p = 0.008), body mass index (+5.5%, p = 0.01), resting energy expenditure (-8.2%, p = 0.006), and %VO2Resp (-44.1%, p = 0.0008) with increase in respiratory quotient (0.79 versus 0.84, p = 0.03) and conversion from prevalent lipid (44.6% versus 34.3%, p = 0.0007) to prevalent carbohydrate (25.2% versus 42.2%, p = 0.0006) metabolism. Thirteen operated on patients discontinued oral steroids, showing the most significant improvements. The remaining 17 experienced significant changes compared with the rehabilitation group despite oral steroids (resting energy expenditure -7.0% versus +4.1%, and %VO2Resp -34.0% versus +0.7%, p = 0.001). Decrease of resting energy expenditure and %VO2Resp correlated with reduction of residual volume (p = 0.02 and p = 0.001) and increment of body mass index (p = 0.03 and p = 0.004)., Conclusions: Lung volume reduction surgery significantly decreased %VO2Resp and resting energy expenditure over respiratory rehabilitation and despite oral steroid therapy. Substrate oxidation changed from prevalent lipid to prevalent carbohydrate. Correlations with residual volume and nutritional status suggest that restoration of respiratory mechanics reduces energy expenditure and approximates metabolism to normal.