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1.
Curr Top Dev Biol ; 119: 349-90, 2016.
Article in English | MEDLINE | ID: mdl-27282030

ABSTRACT

As humans migrated across the world, they encountered new environments requiring them to adapt to new challenges that presented themselves. The distribution of human phenotypes observed today is the result of this continuous adaptation, via biological/physiological and cultural means, and also by the modification of cultural practices, which leads to biological changes. In this chapter, we examine a number of adaptive traits and the roles played by their genetic and environmental determinants. We have selected a few traits used for human identification purposes (externally visible characteristics), associated with human metabolism and linked to a shift in subsistence method and food consumption. We discuss the evolutionary processes that have affected the temporal and spatial distribution of these traits, including natural, sexual, and cultural selection.


Subject(s)
Biological Evolution , Genetic Variation , Adaptation, Biological/genetics , Altitude Sickness/genetics , Body Mass Index , Body Size/genetics , Body Weight/genetics , Eye Color/genetics , Female , Hair Color/genetics , Humans , Lactase/genetics , Male , Phenotype , Selection, Genetic , Skin Pigmentation/genetics , Visual Perception
2.
Eur Respir J ; 39(2): 352-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22183478

ABSTRACT

Some patients with idiopathic pulmonary fibrosis experience acute exacerbations in their respiratory status leading to substantial morbidity and mortality. Occult aspiration of gastric contents has been proposed as one possible mechanism leading to these acute exacerbations. We sought to determine whether pepsin, a marker of gastric aspiration, is elevated in bronchoalveolar lavage fluid obtained from patients during acute exacerbation of idiopathic pulmonary fibrosis, compared with that obtained in stable disease. Lavage samples were obtained in a case-control study of well-characterised patients. Acute exacerbation was defined using standard criteria. Levels of lavage pepsin were compared in cases and controls, and were correlated with clinical features and disease course. 24 cases with acute exacerbations and 30 stable controls were identified. There were no significant differences in baseline demographics between the two groups. Pepsin level was an indicator of acute exacerbation status (p=0.04). On average, pepsin appeared higher in patients with acute exacerbations compared with stable controls. This difference was driven by a subgroup of eight patients (33%) with pepsin levels ≥70 ng·mL(-1). Pepsin level was not an independent predictor of survival time. These results suggest occult aspiration may play a role in some cases of acute exacerbation of idiopathic pulmonary fibrosis.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Idiopathic Pulmonary Fibrosis/metabolism , Idiopathic Pulmonary Fibrosis/mortality , Pepsin A/metabolism , Respiratory Aspiration/metabolism , Respiratory Aspiration/mortality , Acute Disease , Aged , Case-Control Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Pepsin A/analysis , Predictive Value of Tests , Radiography , Respiratory Aspiration/diagnostic imaging , Survival Analysis
3.
Eur Respir J ; 35(1): 118-23, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19679600

ABSTRACT

No therapy is known to improve health-related quality of life (HRQoL) or dyspnoea in patients with idiopathic pulmonary fibrosis. The present study investigated longitudinal changes in HRQoL and dyspnoea and explored the effects of bosentan on these end-points during the Bosentan Use in Interstitial Lung Disease (BUILD)-1 trial. In total, 154 subjects received oral bosentan (n = 71) or placebo (n = 83). Changes in HRQoL and dyspnoea from baseline to month (M) 6 and up to M12 were measured using the St George's Respiratory Questionnaire (SGRQ), 36-item short-form health survey (SF-36), Transition Dyspnoea Index and Borg dyspnoea index. Overall, minimal changes occurred in measures of HRQoL and dyspnoea among placebo-treated subjects during the study. The effects of bosentan treatment on HRQoL and dyspnoea in the all-treated population were minimal. However, in the subset of subjects who had undergone surgical lung biopsy for diagnosis of idiopathic pulmonary fibrosis, treatment effects were observed up to M12 in the impact domain of the SGRQ and the physical functioning, general health and role emotional domains of the SF-36. HRQoL and dyspnoea changed minimally during the course of the present study. Observations from exploratory analyses suggested benefits of bosentan on HRQoL among patients who had undergone surgical lung biopsy for diagnosis, and they merit further investigation.


Subject(s)
Dyspnea/drug therapy , Dyspnea/etiology , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , Quality of Life , Sulfonamides/therapeutic use , Bosentan , Humans
4.
Eur Respir J ; 35(6): 1322-8, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19996193

ABSTRACT

Interstitial lung disease is a common manifestation of rheumatoid arthritis; however, little is known about factors that influence its prognosis. The aim of the present study was to determine whether or not the usual interstitial pneumonia pattern found on high-resolution computed tomography (HRCT) is of prognostic significance in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients with RA-ILD were identified retrospectively (n = 82). The relationship of a definite usual interstitial pneumonia pattern on HRCT to survival was determined and compared to that in a cohort of patients with radiologically diagnosed idiopathic pulmonary fibrosis (n = 51). A definite usual interstitial pneumonia pattern was seen in 20 (24%) out of 82 patients with RA-ILD. These patients showed worse survival than those without this pattern (median survival 3.2 versus 6.6 yrs), and a similar survival to those with idiopathic pulmonary fibrosis. On multivariate analysis, a definite usual interstitial pneumonia pattern on HRCT was associated with worse survival (hazard ratio of 2.3). Analysis of specific HRCT features demonstrated that traction bronchiectasis and honeycomb fibrosis were associated with worse survival (hazard ratio of 2.6 and 2.1, respectively). Female sex (hazard ratio of 0.30) and a higher baseline diffusing capacity of the lung for carbon monoxide (hazard ratio of 0.96) were associated with better survival. A definite usual interstitial pneumonia pattern on HRCT has important prognostic implications in RA-ILD.


Subject(s)
Arthritis, Rheumatoid/mortality , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/mortality , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/mortality , Aged , Aged, 80 and over , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Female , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Kaplan-Meier Estimate , Lung Diseases, Interstitial/drug therapy , Male , Methotrexate/therapeutic use , Middle Aged , Predictive Value of Tests , Prednisone/therapeutic use , Prognosis , Retrospective Studies , Tomography, X-Ray Computed
5.
Sarcoidosis Vasc Diffuse Lung Dis ; 26(2): 92-7, 2009 Jul.
Article in English | MEDLINE | ID: mdl-20560289

ABSTRACT

BACKGROUND: Fatigue is a major problem in sarcoidosis. Fatigue has mainly been examined in patients from The Netherlands. OBJECTIVE: The aims of the study were to establish the prevalence of fatigue in US and Dutch patients and to determine whether fatigue was related to the common demographic and clinical parameters. DESIGN: Two patients groups were studied: Dutch outpatients at Maastricht University Medical Center in The Netherlands (n = 121) and US patients at the University of Cincinnati Medical Center in the USA (n = 126). Both groups completed the Fatigue Assessment Scale. Clinical data were gathered from the patients' medical files. RESULTS: The prevalence of fatigue was similar in the US and Dutch patients, but more severe in the latter group. Fatigue was unrelated to demographic and clinical parameters in the total group. However, when examining the US and Dutch patients separately, fatigue was associated with age, extrapulmonary involvement and drug use in the US group. CONCLUSIONS: Dutch patients report more severe fatigue compared with US patients. Interestingly, fatigue was related to clinical and demographical parameters in the US patients, although no such relationships was found in the Dutch patients.


Subject(s)
Fatigue/epidemiology , Sarcoidosis/complications , Adult , Aged , Aged, 80 and over , Fatigue/etiology , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Prevalence , Sarcoidosis/epidemiology , United States/epidemiology
7.
Thorax ; 63(3): 285-7, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18308964

ABSTRACT

Improved survival from idiopathic pulmonary fibrosis (IPF) is dependent on better understanding of the epidemiology of the disease, its diagnostic spectrum in global terms and an analysis of outcomes from emerging therapies at a significant level. Outside major lung transplant centres, few institutions have significant numbers to provide this information. Relevant examples exist to justify the establishment of registry data to achieve these aims. The gains seen in cystic fibrosis, lymphangioleiomyomatosis and lung transplantation over the past decade stem from optimisation of treatment plans through registry data. We advocate for an international registry to achieve better outcomes in IPF.


Subject(s)
Pulmonary Fibrosis/epidemiology , Registries , Humans , International Cooperation
8.
Eur Respir J ; 29(1): 210-4, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16870664

ABSTRACT

An association of neurofibromatosis with diffuse lung disease (NF-DLD) has been described, but its true prevalence and characteristics remain unclear. The objective of the present study was to define diffuse lung disease in patients with neurofibromatosis. A retrospective case series and literature review in a tertiary care academic medical centre is reported in which medical records, chest radiographs and high-resolution computed tomography (HRCT) scans were reviewed. A total of 55 adult patients with neurofibromatosis were identified, three of whom had NF-DLD. A literature review revealed 16 articles reporting 61 additional cases, yielding a total of 64 NF-DLD cases. The mean age of patients was 50 yrs. Males outnumbered females; most reported dyspnoea. Of the 16 subjects with documented smoking histories, 12 were ever-smokers. Eight patients had HRCT scan results demonstrating ground-glass opacities (37%), bibasilar reticular opacities (50%), bullae (50%), cysts (25%) and emphysema (25%); none had honeycombing. A group of 14 patients had surgical biopsy results that showed findings of interstitial fibrosis (100%) and interstitial inflammation (93%). In conclusion, neurofibromatosis with diffuse lung disease is a definable clinical entity, characterised by upper lobe cystic and bullous disease and lower lobe fibrosis. Its relationship to smoking remains unclear.


Subject(s)
Lung Diseases/diagnostic imaging , Neurofibromatoses/diagnostic imaging , Aged , Female , Humans , Lung Diseases/pathology , Male , Middle Aged , Neurofibromatoses/pathology , Radiography , Respiratory Function Tests
9.
Ann Rheum Dis ; 65(5): 581-4, 2006 May.
Article in English | MEDLINE | ID: mdl-16150789

ABSTRACT

OBJECTIVE: To determine whether exposure to tobacco smoke is associated with double stranded DNA (dsDNA) seropositivity in patients with systemic lupus erythematosus (SLE). METHODS: Medical record review was used to confirm the diagnosis of SLE and evaluate dsDNA antibody status. Smoking status at the time of autoantibody testing was assessed by patients' questionnaire responses. Multivariate regression analysis was used to determine whether exposure to tobacco smoke is associated with dsDNA seropositivity, while controlling for sex and age at SLE diagnosis. RESULTS: A significantly higher risk of dsDNA seropositivity in current smokers than never smokers (odds ratio (OR) = 4.0, 95% confidence interval (CI) 1.6 to 10.4) was shown by multivariate analysis. Current smokers were found to be at higher risk for dsDNA seropositivity than former smokers (OR = 3.0, 95% CI 1.3 to 7.1). The association between current smoking and dsDNA seropositivity remained significant after adjustment for sex, age at SLE diagnosis, amount smoked, age when smoking began, and the duration of smoking cessation (for former smokers). CONCLUSION: The association of smoking with dsDNA seropositivity provides insight into the potential mechanisms underlying autoantibody formation. This information may also serve as a possible point of intervention to prevent disease or target treatment.


Subject(s)
Antibodies, Antinuclear/biosynthesis , DNA/immunology , Lupus Erythematosus, Systemic/etiology , Smoking/adverse effects , Adult , Female , Humans , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Regression Analysis , Retrospective Studies , Smoking/immunology , Smoking Cessation , Time Factors
12.
Eur Respir J ; 19(3): 439-46, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11936520

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials. The goals of this study were to determine whether serum levels of surfactant protein-A (SP-A) or surfactant protein-D (SP-D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP-A or SP-D levels predict outcome in patients with IPF. The authors found that serum SP-A and SP-D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP-D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP-A and SP-D levels were highly predictive of survival in patients with IPF. This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins-A and -D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.


Subject(s)
Glycoproteins/analysis , Proteolipids/analysis , Pulmonary Fibrosis/diagnosis , Pulmonary Surfactants/analysis , Sarcoidosis, Pulmonary/diagnosis , Adult , Aged , Biomarkers/analysis , Cohort Studies , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Glycoproteins/blood , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Prospective Studies , Pulmonary Fibrosis/blood , Pulmonary Fibrosis/mortality , Pulmonary Surfactant-Associated Protein D , Pulmonary Surfactants/blood , Reference Values , Sarcoidosis, Pulmonary/blood , Sarcoidosis, Pulmonary/mortality , Sensitivity and Specificity , Severity of Illness Index , Survival Analysis
14.
Am J Respir Crit Care Med ; 164(6): 1025-32, 2001 Sep 15.
Article in English | MEDLINE | ID: mdl-11587991

ABSTRACT

It is hypothesized that the extent and severity of fibrosis and cellularity found on lung biopsy determine the prognosis and response to therapy in idiopathic pulmonary fibrosis (IPF). The objective of this study was to determine which histopathologic features predict survival in IPF. We prospectively studied 87 patients with usual interstitial pneumonia (UIP) confirmed by surgical lung biopsy. Four pathologists independently graded the extent and severity of specific histopathologic features. We used Cox proportional-hazards models to assess the effect of histopathologic patterns on patients' survival. The effects of age, sex, and smoking were also included in the analysis. Sixty-three patients died during the 17-yr study period. Survival was longer in subjects with lesser degrees of granulation/connective tissue deposition (fibroblastic foci). The degree of alveolar space cellularity, alveolar wall fibrosis, and cellularity did not affect survival. A history of cigarette smoking, the level of dyspnea, and the degree of lung stiffness at presentation were also shown to be independent factors predicting survival. The extent of fibroblastic foci present on lung biopsy predicts survival in IPF. These findings support the hypothesis that the critical pathway to end-stage fibrosis is not "alveolitis" but rather the ongoing epithelial damage and repair process associated with persistent fibroblastic proliferation. Controlling these processes, rather than stopping inflammation, appears most important in preventing progressive disease and the fatal outcome common in IPF.


Subject(s)
Lung Diseases, Interstitial/mortality , Lung Diseases, Interstitial/pathology , Pulmonary Fibrosis/mortality , Pulmonary Fibrosis/pathology , Adult , Age Factors , Aged , Biopsy , Female , Humans , Lung/pathology , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Prospective Studies , Pulmonary Fibrosis/physiopathology , Pulmonary Gas Exchange , Respiratory Function Tests , Sex Factors , Smoking/physiopathology , Survival Analysis , Time Factors
15.
Am J Respir Crit Care Med ; 164(7): 1171-81, 2001 Oct 01.
Article in English | MEDLINE | ID: mdl-11673205

ABSTRACT

Our purpose was to identify clinical, radiological and physiological (CRP) determinants of survival and to develop a CRP scoring system that predicts survival in newly diagnosed cases of idiopathic pulmonary fibrosis (IPF). The study population consisted of 238 patients with biopsy confirmed usual interstitial pneumonia. For each patient, clinical manifestations, chest radiographs, and pulmonary physiology were prospectively assessed. We used Cox proportional-hazards models to assess the effect of these parameters on survival. The effects of age and smoking were included in the analysis. Survival was related to age, smoking status (longer in current smokers), clubbing, the extent of interstitial opacities and presence of pulmonary hypertension on the chest radiograph, reduced lung volume, and abnormal gas exchange during maximal exercise. A mathematical CRP score for predicting survival was derived from these parameters. We showed that this CRP score correlated with the extent and severity of the important histopathologic features of IPF, i.e., fibrosis, cellularity, the granulation/connective tissue deposition, and the total pathologic derangement. Using these models, clinicians are in a better position to provide prognostic information to patients with IPF and to improve the selection of the most appropriate patients for lung transplantation or other standard or novel therapeutic interventions.


Subject(s)
Pulmonary Fibrosis/mortality , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged , Models, Statistical , Multivariate Analysis , Prognosis , Prospective Studies , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/physiopathology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/mortality , Survival Analysis , Survival Rate
16.
J Exp Psychol Anim Behav Process ; 27(3): 219-38, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11497322

ABSTRACT

Brief-moderate shock (3, 0.75 s, 1.0 mA) has opposite effects on different measures of pain, inducing antinociception on the tail-flick test while lowering vocalization thresholds to shock and heat (hyperalgesia) and enhancing fear conditioned by a gridshock unconditioned stimulus (US). This study examined the generality of shock-induced hyperalgesia under a range of conditions and explored parallels to sensitized startle. Reduced vocalization thresholds to shock and antinociception emerged at a similar shock intensity. Severe shocks (3, 25 s, 1.0 mA or 3, 2 s, 3.0 mA) lowered vocalization threshold to shock but increased vocalization and motor thresholds to heat and undermined fear conditioned by a gridshock or a startling tone US. All shock schedules facilitated startle, but only brief-moderate shock inflated fear conditioning. The findings suggest that brief-moderate shock enhances the affective impact of aversive stimuli, whereas severe shocks attenuate pain.


Subject(s)
Hyperalgesia/etiology , Shock/complications , Affect , Animals , Behavior, Animal/physiology , Conditioning, Psychological , Fear , Hyperalgesia/diagnosis , Learning , Male , Nociceptors/physiology , Rats , Rats, Sprague-Dawley , Reflex, Startle/physiology , Vocalization, Animal/physiology
17.
Am J Respir Crit Care Med ; 164(2): 193-6, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11463586

ABSTRACT

It is not known if a surgical lung biopsy is necessary in all patients for the diagnosis of idiopathic pulmonary fibrosis (IPF). We conducted a blinded, prospective study at eight referring centers. Initially, cases were evaluated by clinical history and examination, transbronchial biopsy, and high-resolution lung computed tomography scans. Pulmonologists at the referring centers then assessed their certainty of the diagnosis of IPF and provided an overall diagnosis, before surgical lung biopsy. The lung biopsies were reviewed by a pathology core and 54 of 91 patients received a pathologic diagnosis of IPF. The positive predictive value of a confident (certain) clinical diagnosis of IPF by the referring centers was 80%. The positive predictive value of a confident clinical diagnosis was higher, when the cases were reviewed by a core of pulmonologists (87%) or radiologists (96%). Lung biopsy was most important for diagnosis in those patients with an uncertain diagnosis and those thought unlikely to have IPF. These studies suggest that clinical and radiologic data that result in a confident diagnosis of IPF by an experienced pulmonologist or radiologist are sufficient to obviate the need for a lung biopsy. Lung biopsy is most helpful when clinical and radiologic data result in an uncertain diagnosis or when patients are thought not to have IPF.


Subject(s)
Pulmonary Fibrosis/pathology , Biopsy , Humans , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity
20.
Ann Intern Med ; 134(2): 136-51, 2001 Jan 16.
Article in English | MEDLINE | ID: mdl-11177318

ABSTRACT

Idiopathic pulmonary fibrosis is a progressive and usually fatal lung disease characterized by fibroblast proliferation and extracellular matrix remodeling, which result in irreversible distortion of the lung's architecture. Although the pathogenetic mechanisms remain to be determined, the prevailing hypothesis holds that fibrosis is preceded and provoked by a chronic inflammatory process that injures the lung and modulates lung fibrogenesis, leading to the end-stage fibrotic scar. However, there is little evidence that inflammation is prominent in early disease, and it is unclear whether inflammation is relevant to the development of the fibrotic process. Evidence suggests that inflammation does not play a pivotal role. Inflammation is not a prominent histopathologic finding, and epithelial injury in the absence of ongoing inflammation is sufficient to stimulate the development of fibrosis. In addition, the inflammatory response to a lung fibrogenic insult is not necessarily related to the fibrotic response. Clinical measurements of inflammation fail to correlate with stage or outcome, and potent anti-inflammatory therapy does not improve outcome. This review presents a growing body of evidence suggesting that idiopathic pulmonary fibrosis involves abnormal wound healing in response to multiple, microscopic sites of ongoing alveolar epithelial injury and activation associated with the formation of patchy fibroblast-myofibroblast foci, which evolve to fibrosis. Progress in understanding the fibrogenic mechanisms in the lung is likely to yield more effective therapies.


Subject(s)
Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/therapy , Anti-Inflammatory Agents/therapeutic use , Disease Progression , Epithelium/pathology , Female , Humans , Inflammation/pathology , Male , Pulmonary Fibrosis/epidemiology , Pulmonary Fibrosis/pathology , Wound Healing/physiology
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