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Fernando J Martinez

Publications and source records attributed to Fernando J Martinez.

54 records · Page 3Linked to original sources
PubMed2004

Enhanced monocyte chemoattractant protein-3/CC chemokine ligand-7 in usual interstitial pneumonia.

Chemokines are increased and may exert effects on both inflammatory and remodeling events in idiopathic pulmonary pneumonia (IIP). Accordingly, we examined the concomitant expression of inflammatory CC chemotactic cytokines or chemokines and their corresponding receptors in surgical lung biopsies obtained at the time of disease diagnosis and pulmonary fibroblasts grown from these biopsies. By gene array analysis, upper and lower lobe biopsies and primary fibroblast lines from patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia, and respiratory bronchiolitis-interstitial lung disease, but not patients without IIP, exhibited CCL7 gene expression. TAQMAN, immunohistochemical, and ELISA analyses confirmed that CCL7 was expressed at significantly higher levels in UIP lung biopsies compared with biopsies from patients with nonspecific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease, and from patients without IIP. Higher levels of CCL7 were present in cultures of IIP fibroblasts compared with non-IIP fibroblasts, and CCL5, a CCR5 agonist, significantly increased the synthesis of CCL7 by UIP fibroblasts. Together, these data suggest that CCL7 is highly expressed in biopsies and pulmonary fibroblast lines obtained from patients with UIP relative to patients with other IIP and patients without IIP, and that this CC chemokine may have a major role in the progression of fibrosis in this IIP patient group.

Adult↗
PubMed2004

Monotherapy versus dual therapy for community-acquired pneumonia in hospitalized patients.

Several medical-specialty professional societies have suggested that combination therapy with a beta -lactam plus a macrolide or doxycycline or monotherapy with a "respiratory quinolone" (i.e., levofloxacin, gatifloxacin, moxifloxacin, or gemifloxacin) are optimal first-line therapy for patients hospitalized with community-acquired pneumonia. These recommendations are based predominantly on retrospective studies that suggest improved rates of morbidity and mortality and hospital length of stay among patients treated in such a fashion. Well-designed, prospective, randomized studies confirming this tenet of therapy have not been published, although numerous prospective studies have provided indirect confirmation. The biological rationale for such a differential response (i.e., favoring combination therapy or fluoroquinolone therapy) includes the immunomodulatory effects of macrolides or more-optimal treatment of primary infection or coinfection with atypical pathogens. Well-designed, prospective, randomized trials are required to best define the effectiveness of combination therapy with a beta -lactam plus macrolide or doxycycline or with a respiratory quinolone in hospitalized patients with community-acquired pneumonia.

Anti-Infective Agents↗
PubMed2004

Acute bronchitis: state of the art diagnosis and therapy.

In managing acute bronchitis, pneumonia or an exacerbation of underlying chronic bronchitis should be excluded. Simple bronchitis is best treated symptomatically while an exacerbation of chronic bronchitis can be treated with antibiotics. Broad spectrum antibiotics are appropriate in selected patients.

Acute Disease↗
PubMed2004

Resting and exercise physiology in interstitial lung diseases.

Interstitial lung diseases (ILDs) are a heterogeneous group of parenchymal pulmonary disorders with varying histologic appearances. Pulmonary function tests have gained a prominent role in the diagnosis and management of patients with these disorders. Although their role in the differential diagnosis of the various ILDs is limited, physiologic measurements are pivotal studies providing clues regarding disease severity, prognosis,and response to therapy.

Diagnosis, Differential↗
PubMed2004

Cigarette smoking in interstitial lung disease: concepts for the internist.

Cigarette smoking is a common cause of lung disease. It is clearly implicated in the development of chronic obstructive pulmonary disease and lung cancer. Importantly, cigarette smoking has also been implicated in the development of interstitial lung diseases such as respiratory bronchiolitis interstitial lung disease, desquamative interstitial pneumonia, pulmonary Langerhans' cell histiocytosis,and idiopathic pulmonary fibrosis. The exact role of cigarette smoking in the development of interstitial lung diseases is still being defined; the relatively low prevalence of interstitial lung disease makes epidemiologic studies difficult.

Humans↗
PubMed2004

Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13 receptor subunit expression in idiopathic interstitial pneumonia.

Abnormal proliferation of pulmonary fibroblasts is a prominent feature of chronic pulmonary fibrotic diseases such as idiopathic interstitial pneumonia (IIP), but it is not presently clear how this proliferative response by lung fibroblasts can be therapeutically modulated. In the present study, we examined whether it was possible to selectively target primary human pulmonary fibroblasts grown out of surgical lung biopsies (SLBs) from IIP patients based on their expression of interleukin-4 receptor (IL-4R) and IL-13R subunits. Pulmonary fibroblast lines cultured from patients with the severest form of IIP, namely usual interstitial pneumonia, exhibited the greatest gene and protein expression of IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2 compared with primary pulmonary fibroblast lines grown from other IIP SLBs and normal SLBs. When exposed to increasing concentrations of a chimeric protein comprised of human IL-13 and a truncated version of Pseudomonas exotoxin (IL13-PE), the proliferation of primary usual interstitial pneumonia fibroblasts was inhibited to a much greater extent compared with fibroblast lines from nonspecific interstitial pneumonia and respiratory bronchiolitis/interstitial lung disease patient groups. Fibroblasts from normal patients exhibited minimal susceptibility to the cytotoxic effect of IL13-PE. IL13-PE-mediated targeting of IIP fibroblasts was dependent on their expression of IL-4Ralpha and IL-13Ralpha2. Thus, these data suggest that the abnormal proliferative properties of human lung fibroblasts from certain IIP patient groups can be modulated in a manner that is dependent on the IL-4 and IL-13 receptor subunit expression by these cells.

Base Sequence↗
PubMed2004

Mechanisms of pulmonary fibrosis.

Tissue injury evokes highly conserved, tightly regulated inflammatory responses and less well-understood host repair responses. Both inflammation and repair involve the recruitment, activation, apoptosis, and eventual clearance of key effector cells. In this review, we propose the concept of pulmonary fibrosis as a dysregulated repair process that is perpetually "turned on" even though classical inflammatory pathways may be dampened or "switched off." Significant regional heterogeneity, with varied histopathological patterns of inflammation and fibrosis, has been observed in individual patients with idiopathic pulmonary fibrosis. We discuss environmental factors and host response factors, such as genetic susceptibility and age, that may influence these varied manifestations. Better understanding of the mechanisms of lung repair, which include alveolar reepithelialization, myofibroblast differentiation/activation, and apoptosis, should offer more effective therapeutic options for progressive pulmonary fibrosis.

Humans↗
PubMed2004

Idiopathic pulmonary fibrosis: emerging concepts on pharmacotherapy.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrosing disease of the distal air spaces of the lung of unknown aetiology. IPF is usually fatal with a median survival of < 3 years. There are currently no effective pharmacotherapeutic agents for the treatment of IPF. In this review, unifying concepts on the pathogenesis of IPF based on understanding of host responses to tissue injury are presented. These host responses involve tightly regulated and contextually orchestrated inflammatory and repair processes. Dysregulation of either of these processes can lead to pathological outcomes. Fibrosis results from an exaggerated or dysregulated repair process that proceeds 'uncontrolled' even after inflammatory responses have subsided. Disease heterogeneity may arise when inflammation and repair are in different (dys)regulatory phases, thus accounting for regional disparity. Usual interstitial pneumonia (UIP), the histopathological correlate of clinical IPF, represents a more fibrotic tissue reaction pattern and for which anti-inflammatory agents are ineffective. Emerging 'antifibrotic' drugs and strategies for UIP/IPF are discussed. The importance of accurately phenotyping a highly heterogeneous disease process that may require individualised and 'combined' therapies is emphasised.

Acetylcysteine↗
PubMed2004

Idiopathic pulmonary fibrosis: pathogenesis and therapeutic approaches.

Idiopathic pulmonary fibrosis (IPF), also termed cryptogenic fibrosing alveolitis, is a clinicopathological syndrome characterised by cough, exertional dyspneoa, basilar crackles, a restrictive defect on pulmonary function tests, honeycombing on high-resolution, thin-section computed tomographic scans and the histological diagnosis of usual interstitial pneumonia on lung biopsy. The course is usually indolent but inexorable. Most patients die of progressive respiratory failure within 3-8 years of the onset of symptoms. Current therapies are of unproven benefit. Although the pathogenesis of IPF has not been elucidated, early concepts focused on lung injury leading to a cycle of chronic alveolar inflammation eventuating in fibrosis and destruction of the lung architecture. Anti-inflammatory therapies employing corticosteroids or immunosuppressive or cytotoxic agents have been disappointing. More recent hypotheses acknowledge that sequential alveolar epithelial cell injury is likely to be a key event in the pathogenesis of IPF, but the cardinal event is an aberrant host response to wound healing. In this context, abnormal epithelial-mesenchymal interactions, altered fibroblast phenotypes, exaggerated fibroblast proliferation, and excessive deposition of collagen and extracellular matrix are pivotal to the fibrotic process. Several clinical trials are currently underway or in the planning stages, and include drugs such as interferon-gamma 1b, pirfenidone, acetylcysteine, etanercept (a tumor necrosis factor-alpha antagonist), bosentan (an endothelin-1 receptor antagonist) and zileuton (a 5-lypoxygenase inhibitor). Future therapeutic strategies should be focused on alveolar epithelial cells aimed at enhancing re-epithelialisation and on fibroblastic/myofibroblastic foci, which play an essential role in the development of IPF. Stem cell progenitors of the alveolar epithelial cells and genetic and epigenetic therapies are attractive future approaches for this and other fibrotic lung disorders.

Clinical Trials as Topic↗
PubMed2004

Clinical implications of macrolide therapy in chronic sinopulmonary diseases.

Macrolides have broad antibacterial spectrum and proven efficacy in the management of respiratory tract infections. Over the past decade there has been progressive interest in these agents for their potential role as tissue modifying, anti-inflammatory agents. Increasingly, the effect of macrolides on numerous cell types has been documented. Preliminary data have suggested a beneficial clinical role of chronic macrolide therapy in selected patients with chronic rhinosinusitis, chronic obstructive pulmonary disease, cystic fibrosis, non-cystic fibrosis bronchiectasis and asthma. This review presents the biological rationale and the available clinical data of chronic macrolide therapy in chronic respiratory tract diseases. When available, the data addressing the presumed mechanisms underlying clinical benefits are presented.

Anti-Bacterial Agents↗
PubMed2003

Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia.

Exercise-induced hypoxia is an index of the severity of interstitial lung disease. We hypothesized that desaturation during a 6-minute walk test would predict mortality for patients with usual interstitial pneumonia (n = 83) and nonspecific interstitial pneumonia (n = 22). Consecutive patients with biopsy-proven disease performed a 6-minute walk test between January 1996 and December 2001. Desaturation was defined as a fall in oxygen saturation to 88% or less during the 6-minute walk test. Desaturation was common (44 of 83 usual interstitial pneumonia and 8 of 22 nonspecific interstitial pneumonia; chi square, p = 0.39). Patients with usual interstitial pneumonia or nonspecific interstitial pneumonia who desaturated had a significantly higher mortality than patients who did not desaturate (respective log-rank tests, p = 0.0018, p = 0.0089). In patients with usual interstitial pneumonia, the presence of desaturation was associated with an increased hazard of death (hazard ratio, 4.2; 95% confidence interval, 1.40, 12.56; p = 0.01) after adjusting for age, sex, smoking, baseline diffusion capacity for carbon monoxide, FVC, and resting saturation. We conclude that knowledge of desaturation during a 6-minute walk test adds prognostic information for patients with usual interstitial pneumonia and nonspecific interstitial pneumonia.

Cohort Studies↗
PubMed2003

Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia.

Idiopathic interstitial pneumonias are a diverse group of lung diseases with varied prognoses. We hypothesized that changes in physiologic and radiographic parameters would predict survival. We retrospectively examined 80 patients with usual interstitial pneumonia and 29 patients with nonspecific interstitial pneumonia. Baseline characteristics were examined together with 6-month change in forced vital capacity, diffusing capacity for carbon monoxide, and ground glass infiltrate and fibrosis on high resolution computed tomography. Patients with usual interstitial pneumonia were more likely to have a statistically significant or marginally significant decline in lung volume, diffusing capacity for carbon monoxide, and an increase in ground glass infiltrates (p < or = 0.08) compared with patients with nonspecific interstitial pneumonia. For patients with usual interstitial pneumonia, change in forced vital capacity was the best physiologic predictor of mortality (p = 0.05). In a multivariate Cox proportional hazards model controlling for histopathologic diagnosis, gender, smoking history, baseline forced vital capacity, and 6-month change in forced vital capacity, a decrease in forced vital capacity remained an independent risk factor for mortality (decrease > 10%; hazard ratio 2.47; 95% confidence interval 1.29, 4.73; p = 0.006). We conclude that a 6-month change in forced vital capacity gives additional prognostic information to baseline features for patients with idiopathic interstitial pneumonia.

Adult↗
PubMed2003

Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease.

A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies from 108 patients with usual interstitial pneumonia (nine with collagen vascular disease) and assigned a score (absent 0, mild 1, moderate 2, and marked 3) for fibroblastic foci. Patients with idiopathic usual interstitial pneumonia had a higher median profusion of fibroblastic foci (1.75 vs. 1.0, p = 0.003). Baseline characteristics were similar, although patients with a collagen vascular disease were younger, had a shorter duration of symptoms, and had a higher percentage of predicted total lung capacity. Profusion of fibroblastic foci was the most discriminative feature for separating idiopathic from collagen vascular disease-associated usual interstitial pneumonia (odds ratio 8.31; 95% confidence interval, 1.98, 59.42; p = 0.002 for a one-unit increase in fibroblastic foci score). No deaths were noted in the collagen vascular disease-associated usual interstitial pneumonia group; 52 deaths occurred in the idiopathic usual interstitial pneumonia group (log rank; p = 0.005). We conclude that patients with collagen vascular disease-associated usual interstitial pneumonia have fewer fibroblastic foci and improved survival.

Analysis of Variance↗
PubMed2003

Patient selection for lung volume reduction surgery.

LVRS represents a valid surgical option for a limited number of patients who have symptomatic emphysema. The results of recent controlled studies have provided a realistic view of LVRS outcomes and yielded a validated algorithm for selection of optimal candidates for surgery. Furthermore, the NETT has provided simultaneously collected cost data that have provided a unique view of the costs and benefits of LVRS in patients who have advanced emphysema. Additional data collection will better define the long-term benefits of such surgical intervention in patients who have COPD.

Algorithms↗
PubMed2002

Clinical relevance of macrolide-resistant Streptococcus pneumoniae for community-acquired pneumonia.

Macrolides are often the first choice for empirical treatment of community-acquired pneumonia. However, macrolide resistance among Streptococcus pneumoniae has escalated at alarming rates in North America and worldwide. Macrolide resistance among pneumococci is primarily due to genetic mutations affecting the ribosomal target site (ermAM) or active drug efflux (mefE). Prior antibiotic exposure is the major risk factor for amplification and perpetuation of resistance. Clonal spread facilitates dissemination of drug-resistant strains. Data assessing the impact of macrolide resistance on clinical outcomes are spare. Many experts believe that the clinical impact is limited. Ribosomal mutations confer high-grade resistance, whereas efflux mutations can likely be overridden in vivo. Favorable pharmacokinetics and pharmacodynamics, high concentrations at sites of infections, and additional properties of macrolides may enhance their efficacy. In this article, we discuss the prevalence of macrolide resistance among S. pneumoniae, risk factors and mechanisms responsible for resistance, therapeutic strategies, and implications for the future.

Anti-Bacterial Agents↗
PubMedDate not supplied

A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia.

The normal fibrinolytic activity within the alveolar space is suppressed in fibrotic lung diseases in part because of increased levels of plasminogen activator inhibitor-1 (PAI-1). Studies with animals have shown that inhibition of the plasminogen system by PAI-1 increases the generation of pulmonary fibrosis. To determine if a similar relationship occurs in human fibrotic lung diseases, we took advantage of a polymorphism (4G/5G) that occurs in the promoter region of the human PAI-1 gene and influences the expression of PAI-1. We hypothesized that the 4G/4G genotype, because of its association with higher levels of PAI-1, would occur in patients with idiopathic interstitial pneumonia more frequently than in a control population. PAI-1 promoter genotype was determined in 88 well-characterized patients with idiopathic interstitial pneumonia consisting of 62 patients with usual interstitial pneumonia and 26 with nonspecific interstitial pneumonia. DNA was extracted from paraffin-embedded biopsy tissue and the genotype identified by polymerase chain reaction and restriction endonuclease digestion. We found that the distribution of PAI-1 genotypes in the idiopathic interstitial pneumonia population was similar to that of a large control population. However, subgroup analysis showed that patients with nonspecific interstitial pneumonia were more likely than the control population to have the promoter genotype (4G/4G) that is associated with higher levels of PAI-1. A similar pattern in PAI-1 polymorphism was not seen in the usual interstitial pneumonia subgroup. The results of this study support the conclusion that PAl-1 expression influences the development of nonspecific interstitial pneumonia in a similar manner to what occurs in animal models of pulmonary fibrosis. Patients with usual interstitial pneumonia did not show the same relationship with PAl-1 genotype.

Female↗