Infection in the intensive care unit: a clinician's view of the role of imaging.
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Humans↗
Biomedical subjects
Charlie Strange
Publications and source records attributed to Charlie Strange.
Cyclophosphamide versus placebo in scleroderma lung disease.
BACKGROUND: We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease. METHODS: At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic high-resolution computed tomography, or both. Patients received oral cyclophosphamide (< or =2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC. RESULTS: Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant. CONCLUSIONS: One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.
Administration, Oral↗
Asthma and allergy in alpha-1 antitrypsin deficiency.
This study was designed to determine the prevalence of asthma and atopy, in a large group of subjects with alpha-1 antitrypsin deficiency (AATD) participating in the Alpha-1 Foundation Research Registry. A survey was mailed to all Registry participants (N=2418) and results were collated by AATD phenotype. Participants with PiZZ deficiency were compared to PiMZ and other phenotypes by nonparametric statistics. Responses were collected from 757 participants (31%). Overall 44.6% (N=338) reported MD diagnosed asthma. Wheezing was reported in 76% with respiratory infections, activity and exposure to dusts, fumes, and allergens as common triggers. Across the three groups reported asthma with a history of allergies was reported from 20% to 25%. Wheezing symptoms were significantly less common in the PiMZ group compared with other groups. Of those reporting asthma, 83% of the PiZZ group (n=192) also reported another chronic obstructive pulmonary disease (COPD) diagnosis compared to 48% of the PiMZ group (n=24). Asthma as the only reported diagnosis was three times more prevalent in the PiMZ group compared with the PiZZ group. Although asthma diagnosis is imprecise in the presence of COPD, the high prevalence of wheezing to allergen and irritant exposures with symptoms of atopy suggests that asthma is common in AATD but usually associated with COPD. Those with AATD who are susceptible to asthma require allergy evaluation and aggressive anti-inflammatory strategies as part of their management.
Adult↗
Genetic testing of minors for alpha1-antitrypsin deficiency.
BACKGROUND: Alpha(1)-antitrypsin deficiency (AATD) is a genetic disorder primarily affecting the lungs and liver of affected individuals, causing severe panlobular emphysema and cirrhosis. OBJECTIVE: To describe the demographics and feasibility of a home test for AATD in children and adolescents. DESIGN: Case series of parents who test their children for AATD. SETTING: Nonprofit supported program in which participants telephoned or e-mailed requests for alpha(1)-antitrypsin testing. PARTICIPANTS: All persons younger than 18 years whose parents or guardians chose to test for AATD from January 1, 2002, to October 1, 2004. INTERVENTIONS: Home-administered finger-stick blood spot test for alpha(1)-antitrypsin genotype and questionnaire. MAIN OUTCOME MEASURES: The alpha(1)-antitrypsin genotypes and questionnaire responses. RESULTS: The Alpha Coded Testing Study tested 422 children and adolescents with a confidential test for AATD. Testing was suggested by a family member in most (76.7%) of the cases and was responsible for the many carrier (PIMZ and PIMS) genotypes (51.9%) in the study. Interest in testing was equally distributed among all ages. Test confidentiality was seen as an important reason to test (64.1% with a Likert scale score of 4-5 on a 5-point scale). Parents and guardians of the minors suggested that testing benefits (mean [SD] Likert score, 3.5 [1.4] on a 5-point scale) were higher than risks (mean [SD] Likert score, 1.7 [1.2]) (P=.001). CONCLUSION: Parents value genetic testing of their children at risk for AATD when testing can be done in a confidential setting.
Adolescent↗
Multi-center study: the biochemical efficacy, safety and tolerability of a new alpha1-proteinase inhibitor, Zemaira.
Augmentation therapy with a plasma derived alpha l-Proteinase Inhibitor (alpha1 -PI) has been demonstrated to be effective in restoring serum Alpha1 -antitrypsin (AAT)* levels in individuals with AAT Deficiency (note: alpha1 PI and AAT are synonymous). The objective of this study was to demonstrate that the steady-state trough serum alphal-PI levels, achieved by a new plasma derived alpha,-PI (Zemaira, study drug, ZLB Behring LLC, King of Prussia, Pennsylvania, USA), were bioequivalent to those achieved by the currently available alpha-PI therapy, Prolastin (control drug, Bayer Corporation, Berkeley, California, USA), and maintained weekly trough serum antigenic alpha1-PI levels above the protective threshold of 11 microM. This multi-center, controlled study randomized a total of 44 subjects to receive either study or control drug for a 10-week double-blind phase. The control group was then crossed over to receive the study drug for the remainder of the study (14 weeks). The difference in mean trough serum antigenic alpha1-PI level between the treatment groups was 1.45 microM (90% CI-2.77, -0.13), signifying bioequivalence. The mean trough serum antigenic alpha1-PI level in the study drug group was greater than the therapeutic threshold of 11 microM, achieving a level of 17.7 microM during the steady-state period. Treatment-related adverse events (AEs) were seen in 7% and 21% of study and control drug treated subjects, respectively. No documented viral transmission occurred. These results demonstrate that the new plasma derived alpha1-PI (Zemaira) is bioequivalent to the currently available product Prolastin, is well tolerated, and safe with respect to the risk of viral transmission.
Adolescent↗
Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit.
OBJECTIVE: Intensive insulin therapy to normalize blood glucose may improve outcome in intensive care unit patients. We prospectively evaluated the implementation of an intensive insulin protocol in medical intensive care patients to identify and overcome obstacles that this complex therapy creates. DESIGN: This prospective, quality assessment study was designed to establish a standard protocol for glucose control in critically ill patients. SETTING: The study took place in the medical intensive care unit at the Medical University of South Carolina, a tertiary care center. PATIENTS: Patients diagnosed with sepsis and two consecutive blood glucose measurements of >120 mg/dL were included in the study. INTERVENTIONS: The protocol, targeting blood glucose of 80-120 mg/dL, was a multidisciplinary initiative involving extensive education of house staff before subject enrollment. Based on predefined criteria, patients were monitored daily for glycemic control, inclusion criteria, and protocol adherence. Protocol improvements were assessed at 6 and 12 months via nursing surveys. MEASUREMENTS AND MAIN RESULTS: Seventy patients receiving insulin infusion for >8 hrs were included in data analysis, accounting for 4,920 glucose readings. Eighty-six hypoglycemic events were recorded, with the number of events decreasing from 7.6% to 0.3% by the final version of the protocol. Average duration on protocol was 6 days, and average time to target range was 5.4 hrs. Identifiable causes of hypoglycemia and survey results led to four protocol revisions by study completion. CONCLUSIONS: In comparison to studies suggesting that normoglycemia is an easily achievable goal, our protocol often recorded glucose values <80 mg/dL, although values <60 mg/dL were rare and usually due to protocol violations. In the interval before automated glucose-sensing insulin infusion devices become available for the intensive care unit, the current protocol is available to assist others in achieving target glucose levels shown to improve mortality rate in an intensive care unit population.
Academic Medical Centers↗
Results of a survey of patients with alpha-1 antitrypsin deficiency.
BACKGROUND: alpha(1)-Antitrypsin deficiency (AATD) is an uncommon genetic disease which occurs in 1-2.5% of Americans with chronic obstructive pulmonary disease (COPD). Little is known about current demographics of AATD. OBJECTIVES: This survey study reviews the clinical characteristics of diseased individuals in North America. METHODS: A survey of members from the mailing lists of US AATD patient support organizations was commissioned with duplicate persons omitted. The survey was mailed to 5,222 unique individuals with AATD. Questionnaires were returned by 1,953 individuals, including 1,810 with severe deficiency, 93 with the carrier state and 41 who were caregivers of others. RESULTS: The majority (81%) of participants reported COPD with symptoms of asthma, chronic bronchitis, and emphysema, usually in combination. The mean age of respondents [53.1 +/- 13.2 (SD) years] is older than the general US population. Lung or liver transplantation was reported by 9% of all respondents (n = 175), including 66 single lung transplants, 68 double lung transplants, and 47 liver transplants. Another 6.6% (n = 128) reported that they were currently on a transplant list. Twenty-one percent of lung transplants report continuing augmentation therapy use. Augmentation use is reported by 75% of those with obstructive lung disease. The majority of patients with liver disease also have COPD. CONCLUSIONS: AATD remains a devastating illness for many of those affected as reflected in a high incidence of transplantation for liver and lung disease.
Adolescent↗
Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiency.
BACKGROUND & AIMS: Alpha 1 -antitrypsin deficiency (AAT) is an autosomal recessive disease that affects 1 in 2500 persons and might lead to cirrhosis. Our study aim was to characterize the liver disease in AAT and identify factors associated with advanced liver disease. METHODS: A cohort of the Alpha-1 Foundation Registry who reported liver disease was surveyed with a liver disease questionnaire to obtain information related to liver disease, liver transplantation, and AAT phenotype. RESULTS: One hundred sixty-five of the 2175 participants in the registry reported a history of jaundice or liver disease, and 139 (84.2%) completed the questionnaire. Of these, 71.3% were PiZZ, 18.0% were PiMZ, and 5.7% did not know their phenotype. Analysis of 104 participants with a known age of diagnosis included 30 participants diagnosed with liver disease before 18 years, of whom 15 had advanced liver disease defined as liver transplantation or listed for liver transplantation. No differences in age, age at diagnosis, gender, race, phenotype, or infant jaundice were identified. Seventy-four participants were diagnosed after age 18 years, of whom 25 had advanced liver disease. In this group, advanced liver disease was associated with male gender ( P = .006) and a greater mean body mass index ( P = .01), but not with race, Pi phenotype, infant jaundice, diabetes, or hypercholesterolemia. Viral hepatitis was more frequently reported in the nontransplant group (34.7% vs 8.0%, P = .01), and the mean daily alcohol use was significantly greater in this group ( P = .04). CONCLUSIONS: Our results suggest that male gender and obesity but not alcohol or viral hepatitis predispose to advanced liver disease in adults with AAT.
Adult↗
Pulmonary hypertension in interstitial lung disease.
PURPOSE OF REVIEW: Exercise impairment and pulmonary hypertension are common features of interstitial lung disease. Antifibrotic therapies for interstitial lung disease remain unproved; therefore, some interest has been focused on treating the pulmonary vascular impairment these diseases. RECENT FINDINGS: Patients with pulmonary hypertension secondary to idiopathic pulmonary fibrosis may have normal resting pulmonary artery pressure, but it often rises with exercise. Exercise impairment in idiopathic pulmonary fibrosis has a strong correlation with the degree of pulmonary artery pressure elevation, and hypoxemia, a hallmark of pulmonary hypertension, strongly correlates with survival. SUMMARY: Small case series have shown that some patients improve on receiving therapy for pulmonary hypertension secondary to interstitial lung disease. These findings suggest that larger treatment trials for medications targeting pulmonary hypertension in interstitial lung disease are warranted.
Exercise Test↗
Mortality in individuals with severe deficiency of alpha1-antitrypsin: findings from the National Heart, Lung, and Blood Institute Registry.
STUDY OBJECTIVE: To clarify the mortality rate and causes of death of individuals with alpha(1)-antitrypsin (AAT) deficiency, the Death Review Committee (DRC) of the National Heart, Lung, and Blood Institute Registry of Individuals with Severe AAT Deficiency reviewed all available medical records regarding the deaths of study subjects during Registry follow-up (up to 7.2 years). METHODS: Individual determinations by each member of the three-person DRC led to consensus judgments regarding the underlying cause and the immediate and contributing causes of death. RESULTS: Of the 1,129 Registry subjects, 204 died (18.1%) [approximately 3%/yr]. Record availability permitted detailed review in 120 decedents, and death certificates were available in 56 of the remaining 84 subjects (67%). Emphysema and cirrhosis were the most common underlying causes of death (72% and 10%, respectively), with malignancy and diverticulitis accounting for 3% of deaths each. To assess attributable mortality, standardized mortality ratio analysis was performed and indicated that excess mortality was ascribable entirely to lung and liver disease. CONCLUSIONS: We conclude that severe AAT deficiency poses a significant threat to health, that severe airflow obstruction is a major determinant of mortality, and that liver and lung disease account for the excess mortality in affected individuals. These findings support current efforts to enhance diagnostic recognition and treatment of AAT-deficient individuals.
Adult↗
Pneumothorax in cystic fibrosis.
BACKGROUND: Spontaneous pneumothorax is a complication that is commonly reported in patients with cystic fibrosis (CF). An understanding of the pathophysiology of this complication and its consequences is important for the management of patients with CF. OBJECTIVE: To identify risk factors associated with pneumothorax and to determine the prognosis of CF patients following an episode of pneumothorax. DESIGN: A retrospective observational cohort study of the National Cystic Fibrosis Patient Registry between the years 1990 and 1999. PATIENTS: The registry contained data on 28,858 patients with CF who had been followed up over those 10 years at CF centers across the United States. RESULTS: Pneumothorax occurred with an average annual incidence of 0.64% and in 3.4% of patients overall. There was no increased occurrence by sex, but CF was more prevalent in older patients (mean [+/- SD] age, 21.9 +/- 9.1 years) with more severe pulmonary impairment (nearly 75% of patients with FEV1 of < 40% predicted). The principal risks associated with an increased occurrence of pneumothorax included the presence of Pseudomonas aeruginosa (odds ratio [OR], 2.3), Burkholderia cepacia (OR, 1.8), or Aspergillus (OR, 1.3) in sputum cultures, FEV1 < 30% predicted (OR, 1.5), enteral feeding (OR, 1.7), Medicaid insurance (OR, 1.1), pancreatic insufficiency (OR, 1.4), allergic bronchopulmonary aspergillosis (OR, 1.5), and massive hemoptysis (OR, 1.4). There is an increased morbidity (eg, increased number of hospitalizations and number of days spent in the hospital) and an increased 2-year mortality rate following pneumothorax. CONCLUSION: Pneumothorax is a serious complication in CF patients, occurring more commonly in older patients with more advanced lung disease. Nearly 1 in 167 patients will experience this complication each year. There is an attributable mortality to the complication and considerable morbidity, resulting in increased health-care utilization and a measurable decline in lung function.
Adolescent↗
Treatment for secondary pulmonary hypertension.
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Humans↗
Delay in diagnosis of alpha1-antitrypsin deficiency: a continuing problem.
BACKGROUND AND STUDY OBJECTIVES: Alpha1-antitrypsin (AAT) deficiency is common but under-recognized. A 1994 mail survey showed a long delay between the onset of symptoms and the initial diagnosis of AAT deficiency. In 2003, we carried out a similar mail survey of AAT-deficient individuals to determine whether any delay in diagnosis experienced by individuals with a more recent diagnosis had become shorter. We also determined whether individuals living near medical centers with an expressed interest in AAT deficiency experienced shorter diagnostic delays than those living at a distance. METHODS: Results from mail surveys of two different cohorts were compared: a 1994 survey of 304 individuals with severe AAT deficiency and a 2003 survey of 1,953 AAT-deficient individuals. In the 2003 survey cohort, diagnostic delay intervals were analyzed by calendar year of initial diagnosis, rural vs urban residence, visit to a liver or lung specialist within the last year, and living within 50 miles of a medical center with particular expertise in AAT deficiency. One thousand nine hundred fifty-three individuals responded to the 2003 mail survey (37.4%). RESULTS: In the 2003 cohort, the mean +/- SD diagnostic delay was 5.6 +/- 8.5 years, compared with 7.2 +/- 8.3 years for the 1994 cohort (p = 0.002). In the 2003 cohort, younger patients and male patients experienced shorter diagnostic delays than older patients and female patients (p < 0.0001 and p = 0.007, respectively). For example, the delay was 6.5 +/- 8.8 years for those born in the 1940s, as compared with 0.43 +/- 1.08 years for those born after 1980. Neither urban residence nor living near a center with expertise in AAT deficiency were associated with a shortened diagnostic delay interval. CONCLUSIONS: Although these results show some improvement in the mean diagnostic delay in the 9-year period separating the two studies, under-recognition of AAT deficiency persists. Diagnostic delay of AAT deficiency is longer in women and in older individuals. Educational efforts are underway to enhance clinicians' diagnostic suspicion of AAT deficiency and permit earlier diagnosis and attendant benefits.
Adult↗
"The lion, the witch and the wardrobe": impact on sibs of individuals with AAT deficiency.
Alpha(1)-antitrypsin (AAT) deficiency is a genetic disorder that may cause serious pulmonary or liver impairment in children or adults. Although genetic sequencing of the AAT gene has only been available for 20 years, analysis of the amount and electrophoretic mobility of the AAT protein has allowed clinical phenotyping for more than 40 years. There have been no studies assessing the psychological impact of having a sib affected by AAT deficiency. Twenty-five participants drawn from the Alpha-1 Research Registry completed a questionnaire and semi-structured interview. Respondents were supportive of testing prior to adulthood for AAT status; 18 thought it was a good idea to test a child, three did not know, and four said children should not be tested, primarily citing insurance concerns. Of those 18 who stated it was a good idea, 14 would test at birth. Knowledge of genetics of AAT deficiency was limited; only 44% of respondents understood the inheritance pattern. We recommend: (1) parents and sibs need help in mourning the loss of children with AAT deficiency; young sibs are at risk for trauma and long-term developmental problems. (2) Teams evaluating donors for liver transplantation should be aggressive in ruling out AAT deficiency prior to invasive testing. (3) Testing should be offered to individuals with a family history of AAT deficiency to obtain the health benefits of lifestyle modification and limit the burden of disease discovery in symptomatic relatives. (4) Awareness of liver disease from AAT deficiency should be increased.
Adult↗
Interstitial lung disease in the patient who has connective tissue disease.
Interstitial lung disease is a common complication of many of the connective tissue diseases. Because the prognosis, degree of reversibility, and optimal therapy differs for each disease presentation, a thorough knowledge of the pulmonary presentations of each connective tissue disease is important. Additionally, the challenge of finding the patient who has occult connective tissue disease in an interstitial lung disease clinic is discussed.
Arthritis, Rheumatoid↗
Long-term effects of inhaled corticosteroids on FEV1 in patients with chronic obstructive pulmonary disease. A meta-analysis.
BACKGROUND: There is no consensus on the effectiveness of inhaled corticosteroids for the treatment of chronic obstructive pulmonary disease (COPD). PURPOSE: To evaluate the long-term effects of inhaled corticosteroids on the rate of FEV1 decline in patients with COPD. DATA SOURCES: MEDLINE, EMBASE, CISCOM, and AMED databases and the Cochrane Library (1966 to December 2002), reference lists from identified articles, and consultation with experts. Searches were not limited to the English language. STUDY SELECTION: Randomized, placebo-controlled trials that examined the rate of FEV1 decline as a primary outcome in patients with COPD. DATA EXTRACTION: Two reviewers independently extracted the data by using predetermined criteria. DATA SYNTHESIS: For the six studies that met the inclusion criteria, the summary estimate for the difference in FEV1 decline between the placebo and treatment groups was -5.0 +/- 3.2 mL/y (95% CI, -11.2 to 1.2 mL/y; P = 0.11). CONCLUSIONS: The use of inhaled corticosteroids was not associated with the rate of FEV1 decline in 3571 patients followed for 24 to 54 months.
Administration, Inhalation↗
Obese man treated with drotrecogin alfa (activated).
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Adult↗
Chest ultrasound for "Dummies".
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Education, Medical, Continuing↗