Michael J. Sheridan

Long-term Course and Prognosis of Idiopathic Pulmonary Fibrosis in the New Millennium

The American Thoracic Society and European Respiratory Society guidelines for the diagnosis and treatment of idiopathic pulmonary fibrosis (IPF) have been published recently. However, the influence, practical application, and utility of the prior consensus statement for IPF have never been evaluated. Demographics, diagnostic criteria, pulmonary function data, and disposition of patients with IPF evaluated at an interstitial lung disease center between 2000 and 2009 were analyzed. Enrollment in clinical drug trials, lung transplantation, and mortality also were assessed. A total of 521 patients with IPF were evaluated, with pulmonary function testing available in 446. In the 64% of patients without surgical lung biopsy, the most common major criterion not fulfilled was bronchoscopy. Lung transplantation was performed in 16.1% of patients, whereas 27.4% of prescreened patients were enrolled in a prospective drug study. Patients with mild, moderate, and severe disease categorized by FVC % predicted had median survivals of 55.6, 38.7, and 27.4 months, respectively. The attrition rate of patients who survived beyond 5 years was attenuated in subsequent years. IPF remains a deadly disease with a poor prognosis. Bronchoscopy does not appear to be required for an accurate diagnosis. A minority of patients were accommodated within a clinical trial or with transplantation. Categorization by baseline FVC % predicted effectively discriminates groups with different long-term outcomes. Our analysis supports the view that the value of statements also can be realized in the subsequent demonstration of their impact on patient management, which might enable further refinements in a continuous, iterative rediscovery process.

Identification of pioneer viridans streptococci in the oral cavity of human neonates.

Three hundred and sixty-seven strains of pioneer streptococci isolated from the mouths of 40 healthy, full-term infants during the first month of life were examined by two taxonomic schemes that incorporated biochemical and physiological characteristics, IgA1 protease production and glycosidase activities. Streptococcus mitis biovar 1 and S. oralis comprised 55.0% of the pioneer streptococci isolated from neonates. S. salivarius constituted 25.3% of the isolates, while S. anginosus, S. mitis biovar 2, S. sanguis and S. gordonii accounted collectively for 11.4%. Difficulties in identifying streptococci were encountered and 8.4% of the 367 isolates could not be assigned to a recognised species.

Antimicrobial prescribing for acute purulent rhinitis in children: a survey of pediatricians and family practitioners.

BACKGROUND The tenet that children with acute purulent rhinitis need not be treated with antibiotics unless drainage persists for 7 to 10 days is taught to medical students and residents in primary care specialties but may not be adhered to in actual clinical practice. Because of the global increase in bacterial resistance stemming largely from the overuse of antibiotics, we sought to determine how acute purulent rhinitis is managed in the primary care setting. METHODS We surveyed all 450 pediatricians (PD) and family practitioners (FP) in northern Virginia who were in active practice in 1994. The survey instrument was a questionnaire containing two clinical vignettes followed by a series of multiple choice or fill-in-the-blanks questions. Initial nonresponders received up to three additional mailings of the same questionnaire. RESULTS There were 346 (77%) evaluable responses. Seventy-one percent of FP and 53% of PD (P = 0.001) immediately prescribed antibiotics for infants with scant, green nasal mucopurulent secretions of 1 day duration; fewer treated an older child immediately (50% FP vs. 24% PD, P < 0.00001). Only 15% of FP vs. 23% of PD (P = 0.07) waited for 7 to 10 days of persistent purulent nasal drainage in infants before prescribing antibiotics. Ninety-four percent of FP and 95% of PD (P = 0.8) indicated that they would prescribe antibiotics immediately for infants with acute purulent rhinitis who attended day care. For otitis-prone children who were not in day care, 86% of FP and 78% of PD (P = 0.02) would also treat without delay. The reasons given for prompt antibiotic therapy were (1) the belief that many untreated patients would develop persistent purulent nasal drainage, (2) concern that acute otitis media would develop, (3) pressure from mothers to prescribe an antibiotic and/or (4) the desire to allow employed parents to return to work earlier. Amoxicillin was the initial choice for 89% of FP vs. 76% of PD (P = 0.003). Most FP (89%) and PD (97%) were concerned about the increase in bacterial resistance rates arising from unnecessary antibiotic prescribing (P = 0.01). CONCLUSIONS Most infants and children with acute purulent rhinitis of short duration were treated with antibiotics despite professed concerns over the spread of bacterial resistance; the practice was more prevalent among FP.

Pistachio Nut Consumption and Serum Lipid Levels

Objective: Clinical and epidemiological studies have reported the beneficial effects of tree nuts and peanuts on serum lipid levels. We studied the effects of consuming 15% of the daily caloric intake in the form of pistachio nuts on the lipid profiles of free-living human subjects with primary, moderate hypercholesterolemia (serum cholesterol greater than 210 mg/dL). Methods: Design: Randomized crossover trial. Setting: Outpatient dietary counseling and blood analysis. Subjects: 15 subjects with moderate hypercholesterolemia. Intervention: Fours weeks of dietary modification with 15% caloric intake from pistachio nuts. Measures of Outcome: Endpoints were serum lipid levels of total cholesterol, HDL-C, LDL-C, VLDL-C, triglycerides and apolipoproteins A-1 and B-100. BMI, blood pressure, and nutrient intake (total energy, fat, protein, and fiber) were also measured at baseline, during, and after dietary intervention. Results: No statistically significant differences were observed for total energy or percent of energy from protein, carbohydrate or fat. On the pistachio nut diet, a statistically significant decrease was seen for percent energy from saturated fat (mean difference, −2.7%; 95% CI, −5.4% to −0.08%; p = 0.04). On the pistachio nut diet, statistically significant increases were seen for percent energy from polyunsaturated fat (mean difference, 6.5%; 95% CI, 4.2% to 8.9%; p<.0001) and fiber intake (mean difference, 15g; 95% CI, 8.4g to 22g; p = 0.0003). On the pistachio diet, statistically significant reductions were seen in TC/HDL-C (mean difference, −0.38; 95% CI, −0.57 to −0.19; p = 0.001), LDL-C/HDL-C (mean difference, −0.40; 95% CI, −0.66 to −0.15; p = 0.004), B-100/A-1 (mean difference, −0.11; 95% CI, −0.19 to −0.03; p = 0.009) and a statistically significant increase was seen in HDL-C (mean difference, 2.3; 95% CI, 0.48 to 4.0; p = 0.02). No statistically significant differences were seen for total cholesterol, triglycerides, LDL-C, VLDL-C, apolipoprotein A-1 or apolipoprotein B-100. No changes were observed in BMI or blood pressure. Conclusion: A diet consisting of 15% of calories as pistachio nuts (about 2–3 ounces per day) over a four week period can favorably improve some lipid profiles in subjects with moderate hypercholesterolemia and may reduce risk of coronary disease.

Adherence and Invasion Studies of Candida albicans Strains, Using In Vitro Models of Esophageal Candidiasis

The adherence of clinical and commensal isolates and reference collection strains of Candida albicans to a human esophageal cell monolayer (HET1-A) and reconstituted human esophageal tissue was compared. Isolates from patients with a severe form of esophageal candidiasis or candidemia adhered to HET1-A cells to a significantly greater extent than did isolates from patients with mild esophageal candidiasis or commensal and reference collection strains. In addition, C. albicans strain SSK21, which lacks the ssk1 response regulator gene of a 2-component signal transduction pathway, adhered less readily to the HET1-A cells than did parental cells or a gene-reconstituted strain. In a reconstituted esophageal tissue model, all clinical strains but not commensal or reference collection strains penetrated the epithelium, albeit at different rates. Hyphal formation following yeast cell adherence to the esophageal tissue was a requirement for invasion. Scanning electron microscopy was also used to confirm the colonization of the esophageal tissues by various strains. These studies indicate that both the HET1-A and the reconstituted esophageal tissue models can be used as in vitro targets to evaluate the adherence phenotype and invasiveness of C. albicans strains.

Thoracic esophageal perforations.

Background Recognition of the importance of early diagnosis and aggressive, definitive surgical intervention has brought about a dramatic decline in mortality related to distal esophageal perforation. Methods We retrospectively analyzed all cases of thoracic esophageal perforation diagnosed at our hospital from September 1, 1979, through April 1, 2001. The study group consisted of 62 patients (43 men) with a mean age of 58.8 years (range, 20–92 yr). Results In the group of 39 patients with early diagnosis (≤24 h), hospital survival was 87%, which increased to 93% when early diagnosis was combined with aggressive surgical treatment. Among the 23 patients with late diagnosis (>24 h), survival approached 70%. Yet, in patients who were treated aggressively with surgery, survival was almost 90% despite delayed diagnosis. Conclusion We recommend aggressive, definitive surgery for thoracic esophageal perforations, whether diagnosed early or late. A variety of options are discussed with regard to complicated presentations.

Selective Mutism: Are Primary Care Physicians Missing the Silence?

To survey parents of children with selective mutism (SM) in regard to (1) the role of the primary care physician in the diagnosis of SM; (2) the social and school consequences of SM; and (3) their opinion of the effectiveness of different treatment modalities, a 39-item written survey was mailed to 27 parents with at least one child diagnosed with SM on the basis of diagnostic and statistical manual IV-text revision (DSM IV-TR) criteria. Twenty-seven parents (100%), with a total of 33 children with SM, completed the survey. There were 24 girls and 9 boys. The mean age when parents had strong concerns about symptoms of SM was 3.8 years, but diagnosis did not occur until nearly a year later. Twenty-three (69.7%) of the children with SM were never diagnosed accurately or referred by their primary care physicians. SM caused important school/social problems for 17 (51.5%) of the children. Speech therapy was provided for 36.4% of children and was thought to have been helpful for 30% of them. Behavior modification was the treatment for 45.5% of children and perceived to be helpful for 66.7% of them. Selective serotonin re-uptake inhibitor pharmacotherapy was prescribed for 17 (51.5%) of the children and believed to be effective for 11 (65%) of them. Primary care physicians in this study rarely diagnosed accurately or referred children with SM in a timely fashion, even though symptoms of the condition were generally very apparent and parents had expressed concern. Behavioral modification, pharmacotherapy with SSRIs, and early intervention are viable treatment options. Early diagnosis is key to preventing long-term effects of this condition.

High Rates of Uninsured Among HCV-Positive Individuals

Background and Goals: There are no published data on the health insurance status of Hepatitis C virus (HCV)-positive individuals. To address this issue, we analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). Study: Individuals 18 years of age and older who participated in NHANES III were included in the study. We determined the rates of health insurance coverage according to HCV status. We also determined healthcare status and health service utilization according to health insurance status among HCV-positive persons. Results: HCV-positive individuals were more likely to be uninsured compared with those who were HCV-negative (29.6% vs. 12.2%, P = 0.0002). Among those with health insurance, HCV-positive individuals were more likely to have government insurance compared with those who were HCV-negative (42.9% vs. 27.6%, P < 0.005). Among HCV-positive individuals, being uninsured was associated with younger age, being unmarried, living in the South, Mexican-American race/ethnicity, and not graduating from high school. Additionally, the uninsured were less likely than their insured counterparts to identify a healthcare facility for sick or routine care, and less likely to have regular contact with a healthcare professional. Conclusions: A high proportion of HCV-positive individuals are uninsured, and many HCV-positive individuals with health insurance have publicly funded insurance. This finding may have implications for access to health care and for liver-related disease outcomes in HCV-positive persons.

Pulmonary artery size as a predictor of pulmonary hypertension and outcomes in patients with chronic obstructive pulmonary disease

RATIONALE The relationship between pulmonary artery size with underlying pulmonary hypertension and mortality remains to be determined in COPD. We sought to evaluate the relationships in a cohort of patients with advanced COPD. METHODS A retrospective study of advanced COPD patients evaluated between 1998 and 2012 was conducted at a tertiary care center. Patients with chest computed tomography images and right heart catheterizations formed the study cohort. The diameters of the pulmonary artery and ascending aorta were measured by independent observers and compared to pulmonary artery pressures. Intermediate-term mortality was evaluated for the 24-month period subsequent to the respective studies. Cox proportional hazards model was used to determine independent effects of variables on survival. RESULTS There were 65 subjects identified, of whom 38 (58%) had pulmonary hypertension. Patients with and without pulmonary hypertension had mean pulmonary artery diameters of 34.4 mm and 29.1 mm, respectively (p = 0.0003). The mean PA:A ratio for those with and without pulmonary hypertension was 1.05 and 0.87, respectively (p = 0.0003). The PA:A ratio was an independent predictor of mortality with a reduced survival in those with a PA:A >1 (p = 0.008). CONCLUSIONS The PA:A ratio is associated with underlying pulmonary hypertension in patients with COPD and is an independent predictor of mortality. This readily available measurement may be a valuable non-invasive screening tool for underlying pulmonary hypertension in COPD patients and appears to impart important independent prognostic information.

The Red Cell Distribution Width as a Prognostic Indicator in Idiopathic Pulmonary Fibrosis

BACKGROUND The course of idiopathic pulmonary fibrosis (IPF) is characterized by variable patterns of disease progression. The red cell distribution width (RDW) is a parameter that is routinely reported with all CBC counts. We sought to test the prognostic usefulness of this parameter in a well-defined cohort of patients with IPF. METHODS CBCs, demographics, and pulmonary function data from patients with IPF evaluated between January 1997 and June 2011 were collated. Patient outcomes were ascertained from the programs database and the Social Security Death Index. RESULTS There were 319 patients with IPF evaluated in whom baseline CBCs were available. The range in the RDW was 11.9 to 21.9 (median 14.1). There were 228 subjects with RDW values ≤ 15 (normal) and 91 patients with RDW values > 15. Patients with normal RDW values had a median survival of 43.1 months compared with 16.3 months for those whose RDW was > 15 (P = .001). There were 198 patients with available serial RDW data. Those patients who had a change in the RDW of less or greater than +0.010/mo had median survivals of 43.0 and 23.9 months, respectively (P = .0246). CONCLUSIONS The RDW is a readily available laboratory test result that may provide important, independent prognostic information at baseline and follow-up in patients with IPF. Further studies are warranted to validate this as a biomarker for IPF outcomes, as well as to define the biologic basis for this association.