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Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene(®)), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods: Four key disease characteristics – environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry – were evaluated in a group of 8784 current and former smokers who were participants in COPDGene(®) Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV(1) > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene(®) 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15–6.48) in those with all 4 disease characteristics. Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

In order to characterise asthma management in a managed care setting, we identified 10,301 patients who were diagnosed with asthma between 1 January 1988 and 31 December 1991 at a group model health maintenance organisation in central Massachusetts, US. We obtained for these patients automated utilisation files containing data on medications, hospitalisations, emergency room visits, office visits, and estimated costs of these services. The medication dispensed to the greatest proportion of patients was beta 2 agonists either by inhalation (56%) or orally (21%). Theophylline was dispensed to 23% of the patients. Maintenance therapy was inhaled anti-inflammatory medication was uncommon, as inhaled corticosteroids (17%) and sodium cromoglycate (cromolyn sodium) [8%] were dispensed to fewer patients than other asthma medications. Among patients who had been hospitalised in the previous year, 36% were presently receiving inhaled corticosteroids, and among patients who used at least one beta 2 agonist metered-dose inhaler per month, 49% were presently receiving inhaled corticosteroids. Economic analyses showed that only 8% of the patients had either a hospital admission or an emergency room visit, but hospital costs among these patients accounted for 25% of the total costs of asthma care. In addition, the top 10% most expensive patients accounted for 42% of the total cost of asthma care. We conclude that a substantial proportion of patients at increased risk of a severe attack, by virtue of having a recent hospitalisation, do not receive maintenance anti-inflammatory therapy, and that hospitalisations among a relatively small proportion of asthma patients contribute significantly to the cost of asthma care.

To measure adherence to inhaled corticosteroid (ICS) therapy using prescription claims and a patient survey, to identify local adverse events (LAEs) from the patient perspective and from medical records, and to evaluate the association between LAEs and adherence to ICS therapy.Survey administration and claims-based and medical record-abstracted data.Patients aged 6 to 64 years with persistent asthma (defined using an established algorithm) and at least 2 ICS prescriptions were selected from a claims database (1999-2006) of a central Massachusetts medical group practice. Prescription claims were used to calculate the ICS medication possession ratio (MPR). A survey obtained information about patient-reported adherence to ICSs using the Morisky scale and a visual analog scale (VAS) and about LAEs using the validated Inhaled Corticosteroid Questionnaire. Medical records of survey respondents were abstracted for LAEs.Among 372 survey respondents, 2.7% met the claims-based measure of good adherence (MPR,or =80%). Patient-reported adherence was much higher; 20.7% of patients were highly adherent based on the Morisky scale (score, 0) and 55.4% based on the VAS (score,or =80%). Medical record review identified 27.2% of patients having at least 1 LAE within 1 year after the ICS index date, but 47.3% of patients reported being bothered at least "quite a lot" by LAEs. Multivariate analysis indicated that unpleasant taste was significantly related to lower adherence based on the Morisky scale (P = .02).Patient-reported adherence and LAEs were higher than those measured from claims or medical records. Unpleasant taste seems to be associated with lower adherence based on the Morisky scale.

The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition.

The effects of treatment with a perfluorochemical emulsion plus carbogen on radiation pneumonitis were examined in a rat model system. Rats received thoracic irradiation (15 Gy) and radiation reactions in the lungs were assessed 25 and 35 days later using bronchoalveolar lavage and histologic assessments. The irradiated lungs showed the expected evidence of acute radiation pneumonitis, including protein leaks and also alveolar infiltrates and interstitial infiltrates. Administration of a perfluoro-chemical emulsion (Fluosol; 15 ml/kg) plus carbogen breathing for 30 min before and during irradiation did not enhance the reactions seen in the irradiated lungs. 32 refs., 3 tabs.

A common side effect of radiotherapy is the development of fibrosis in the irradiated tissue. To study the mechanisms of this fibrogenic response, we developed a model system of whole-lung radiation in the rat and studied the evolution of injury by assessment of the cells and protein recovered by lavage. Once the pattern of injury was known, we attempted to modulate this reaction by administering the cytokine interferon-gamma (IFN-gamma). Rats received 15 Gy radiation to the whole thorax and were studied by lung lavage at intervals of 1 to 35 days after radiation. The effect of radiation was an initial (24 h) leak of protein, unaccompanied by cellular alterations, that resolved by 48 h. This was followed 2 wk later by a phase of inflammatory cell recruitment and more significant protein leak. A third phase of increase in inflammatory cells and further increase in protein flux was noted at Day 35. A significant cellular infiltrate was seen in lung sections obtained from animals treated in parallel experiments. IFN-gamma was given by osmotic pump from Day 0 to Day 35. This treatment significantly attenuated the PMN recruitment and protein leak (p0.002 and 0.01, respectively) at Days 25 and 35. Histologic sections demonstrated reduced alveolar cellularity and exudate at Day 25 (p0.05); however, significant numbers of inflammatory cells and exudate were present in irradiated and IFN-gamma-treated animals at Day 35. These data indicate that inflammatory cell recruitment may play a role in the lung injury following radiation. Furthermore, these preliminary data indicate that a cytokine blocks this reaction.

Structural changes occur in the respiratory system with advancing age. Lung elasticity decreases, stiffness of the chest wall increases, and respiratory muscle strength declines. These alterations contribute to gradual, but progressive, reductions in forced vital capacity, expiratory flow rates, diffusing capacity, gas exchange, ventilatory drive, and respiratory sensation. Cigarette smoking accelerates the age-related decline in flow rates. Understanding the effects of aging on the lung is important in order to distinguish pathologic changes from changes that are part of the normal aging process.

The purpose of this investigation was to evaluate the cardiovascular responses to rowing. In the first part of the study, heart rate (HR) and cardiac output (Q) were measured at rest and at three steady-state exercise levels on the variable-resistance rowing ergometer in 10 female and 11 male subjects. Q was determined non-invasively by the equilibration method of CO2 re-breathing, and stroke volume (SV) was calculated. Subjects varied in rowing ability from healthy, inexperienced rowers to competitive athletes. The linear relationships between Q and oxygen consumption for the women (r = 0.57; P less than 0.001; slope = 5.2 +/- 1.1) (mean +/- SD) and the men (r = 0.58; P less than 0.001; slope = 6.1 +/- 1.4) were similar to published values for other types of upright exercises. For both mean and women, SV increased from rest to the first level of exercise, and then reached a plateau at or before the second exercise intensity. Between the second and third levels of exercise, SV decreased significantly in the female subjects (107 +/- 18 vs 94 +/- 16 ml; P less than 0.05), but not in the male subjects (128 +/- 1 1 vs 126 +/- 15 ml; P = not statistically significant). In the second part of the study, HR, Q, and SV were compared on the cycle and rowing ergometers on successive days in eight additional subjects. At similar levels of oxygen consumption and Q, HR was significantly higher, and SV was significantly lower during rowing exercise than with cycle exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

• The optimal time to begin oral anticoagulation therapy with warfarin sodium in the treatment of acute pulmonary embolism has not been defined. To evaluate the relative cost, efficacy, and safety of early initiation of warfarin therapy, we reviewed the medical records of 38 patients with angiographically proven pulmonary embolism. Patients were divided into two groups: those who received warfarin early (≤3 days after initial heparin sodium bolus, n=17) and those who were treated late (>3 days after initial heparin bolus, n=21). After three months of follow-up, there was a similar incidence of mortality, recurrent pulmonary embolism, and bleeding complications in both treatment groups. Length of hospitalization was substantially less in the early group (9.6 ± vs 11.8±2.1 days). Early warfarin therapy in the treatment of acute pulmonary embolism appears to be both cost-effective and safe. A prospective multicenter controlled trial should be performed. ( Arch Intern Med 1987;147:1469-1473)