RESUMEN
Goblet cell hyperplasia is a common feature of chronic obstructive pulmonary disease (COPD) airways, but the mechanisms that underlie this epithelial remodelling in COPD are not understood. Based on our previous finding of hypoxia-inducible factor-1α (HIF-1α) nuclear localization in large airways from patients with COPD, we investigated whether hypoxia-inducible signalling could influence the development of goblet cell hyperplasia. We evaluated large airway samples obtained from 18 lifelong non-smokers and 13 former smokers without COPD, and 45 former smokers with COPD. In these specimens, HIF-1α nuclear staining occurred almost exclusively in COPD patients in areas of airway remodelling. In COPD patients, 93.2 ± 3.9% (range 65-100%) of goblet cells were HIF-1α positive in areas of goblet cell hyperplasia, whereas nuclear HIF-1α was not detected in individuals without COPD or in normal-appearing pseudostratified epithelium from COPD patients. To determine the direct effects of hypoxia-inducible signalling on epithelial cell differentiation in vitro, human bronchial epithelial cells (HBECs) were grown in air-liquid interface cultures under hypoxia (1% O(2)) or following treatment with a selective HIF-1α stabilizer, (2R)-[(4-biphenylylsulphonyl)amino]-N-hydroxy-3-phenyl-propionamide (BiPS). HBECs grown in hypoxia or with BiPS treatment were characterized by HIF-1α activation, carbonic anhydrase IX expression, mucus-producing cell hyperplasia and increased expression of MUC5AC. Analysis of signal transduction pathways in cells with HIF-1α activation showed increased ERK1/2 phosphorylation without activation of epidermal growth factor receptor, Ras, PI3K-Akt or STAT6. These data indicate an important effect of hypoxia-inducible signalling on airway epithelial cell differentiation and identify a new potential target to limit mucus production in COPD.
Asunto(s)
Bronquios/patología , Células Caliciformes/patología , Factor 1 Inducible por Hipoxia/fisiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Mucosa Respiratoria/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Bronquios/metabolismo , Diferenciación Celular/fisiología , Hipoxia de la Célula/fisiología , Células Cultivadas , Activación Enzimática/fisiología , Femenino , Células Caliciformes/metabolismo , Humanos , Hiperplasia/metabolismo , Hiperplasia/patología , Masculino , Persona de Mediana Edad , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Mucina 5AC/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Mucosa Respiratoria/metabolismo , Transducción de Señal/fisiología , Adulto JovenRESUMEN
RATIONALE: Although airway inflammation can persist for years after smoking cessation in patients with chronic obstructive pulmonary disease (COPD), the mechanisms of persistent inflammation are largely unknown. OBJECTIVES: We investigated relationships between bronchial epithelial remodeling, polymeric immunoglobulin receptor (pIgR) expression, secretory IgA (SIgA), airway inflammation, and mural remodeling in COPD. METHODS: Lung tissue specimens and bronchoalveolar lavage were obtained from lifetime nonsmokers and former smokers with or without COPD. Epithelial structural changes were quantified by morphometric analysis. Expression of pIgR was determined by immunostaining and real-time polymerase chain reaction. Immunohistochemistry was performed for IgA, CD4 and CD8 lymphocytes, and cytomegalovirus and Epstein-Barr virus antigens. Total IgA and SIgA were measured by ELISA and IgA transcytosis was studied using cultured human bronchial epithelial cells. MEASUREMENTS AND MAIN RESULTS: Areas of bronchial mucosa covered by normal pseudostratified ciliated epithelium were characterized by pIgR expression with SIgA present on the mucosal surface. In contrast, areas of bronchial epithelial remodeling had reduced pIgR expression, localized SIgA deficiency, and increased CD4(+) and CD8(+) lymphocyte infiltration. In small airways (<2 mm), these changes were associated with presence of herpesvirus antigens, airway wall remodeling, and airflow limitation in patients with COPD. Patients with COPD had reduced SIgA in bronchoalveolar lavage. Air-liquid interface epithelial cell cultures revealed that complete epithelial differentiation was required for normal pIgR expression and IgA transcytosis. CONCLUSIONS: Our findings indicate that epithelial structural abnormalities lead to localized SIgA deficiency in COPD airways. Impaired mucosal immunity may contribute to persistent airway inflammation and progressive airway remodeling in COPD.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Inmunoglobulina A Secretora/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Receptores de Inmunoglobulina Polimérica/inmunología , Fumar/efectos adversos , Bronquios/patología , Bronquios/fisiopatología , Bronquios/virología , Citomegalovirus/aislamiento & purificación , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunoglobulina A Secretora/análisis , Inflamación/inmunología , Inflamación/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Sistema Respiratorio/inmunología , Fumar/inmunología , TiempoRESUMEN
Current guidelines recommend inhalation therapy as the preferred route of drug administration for treating patients with chronic obstructive pulmonary disease (COPD). Inhalation devices consist of nebulizers and handheld inhalers, such as dry-powder inhalers (DPIs), pressurized metered-dose inhalers (pMDIs), and soft mist inhalers (SMIs). Although pMDIs, DPIs and SMIs may be appropriate for most patients with COPD, certain patient populations may have challenges with these devices. Patients who have cognitive, neuromuscular, or ventilatory impairments (and receive limited assistance from caregivers), as well as those with suboptimal peak inspiratory flow may not derive the full benefit from handheld inhalers. A considerable number of patients are not capable of producing a peak inspiratory flow rate to overcome the internal resistance of DPIs. Furthermore, patients may have difficulty coordinating inhalation with device actuation, which is required for pMDIs and SMIs. However, inhalation devices such as spacers and valved holding chambers can be used with pMDIs to increase the efficiency of aerosol delivery. Nebulized treatment provides patients with COPD an alternative administration route that avoids the need for inspiratory flow, manual dexterity, or complex hand-breath coordination. The recent approval of two nebulized long-acting muscarinic antagonists has added to the extensive range of nebulized therapies in COPD. Furthermore, with the availability of quieter and more portable nebulizer devices, nebulization may be a useful treatment option in the management of certain patient populations with COPD. The aim of this narrative review was to highlight recent updates and the treatment landscape in nebulized therapy and COPD. We first discuss the pathophysiology of patients with COPD and inhalation device considerations. Second, we review the updates on recently approved and newly marketed nebulized treatments, nebulized treatments currently in development, and technological advances in nebulizer devices. Finally, we discuss the current applications of nebulized therapy in patients with COPD.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Broncodilatadores/uso terapéutico , Diseño de Equipo , Humanos , Inhaladores de Dosis Medida , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológicoRESUMEN
BACKGROUND: Information is limited on long-term outcomes after preemptive use of ganciclovir to control cytomegalovirus (CMV) infection in lung transplantation. METHODS: We studied 78 lung recipients who received antithymocyte globulin induction from 1994 to 2000. All patients received six months of oral acyclovir (800 mg TID). This was interrupted three wk post transplantation for a two-wk course of IV ganciclovir. Additional courses of ganciclovir were administered based on serial virological monitoring. CMV-mismatched patients (R-D+) also received four doses of CMV immunoglobulin between weeks 2 and 8. RESULTS: The one yr cumulative risk of CMV disease was 2% (1/61) in CMV seropositive (R+) patients, but was 37% (6/17) in R-D+ patients (p < 0.0001). Over 4.3 yr of follow-up, patients with CMV infection developed more chronic graft dysfunction caused by bronchiolitis obliterans or bronchiolitis obliterans syndrome than patients without CMV infection (p = 0.012). This effect was also apparent in the subgroup of R+ recipients (p = 0.043). Acute rejection and overall survival were not associated with CMV infection. CONCLUSIONS: The use of prophylactic acyclovir and short preemptive courses of ganciclovir effectively controlled CMV disease in R+ patients, but was a relative failure in R-D+ patients. CMV infection was significantly associated with chronic graft dysfunction, even in R+ recipients who had good control of CMV symptoms.
Asunto(s)
Antivirales/administración & dosificación , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/administración & dosificación , Trasplante de Corazón-Pulmón , Aciclovir/administración & dosificación , Adolescente , Adulto , Anciano , Quimioprevención , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/transmisión , Funcionamiento Retardado del Injerto/virología , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Donantes de Tejidos , Adulto JovenRESUMEN
Fibrosing mediastinitis with bronchial artery hypervascularity is a rare cause of massive hemoptysis. Conventional therapies for massive hemoptysis include pulmonary or bronchial artery embolization, endobronchial tamponade, or lung resection. A patient with fibrosing mediastinitis presented with refractory massive hemoptysis associated with bronchial hypervascularity and was treated with external-beam radiotherapy (XRT). The application of XRT for massive hemoptysis in malignant and nonmalignant disease of the thorax is discussed.
Asunto(s)
Hemoptisis/radioterapia , Mediastinitis/radioterapia , Fibrosis Pulmonar/radioterapia , Hemoptisis/etiología , Humanos , Masculino , Mediastinitis/complicaciones , Persona de Mediana Edad , Fibrosis Pulmonar/complicacionesRESUMEN
In airway remodeling that occurs in association with chronic obstructive pulmonary disease (COPD), the relationship between the subepithelium and structural changes of the bronchial epithelium is not well defined. To investigate whether the subepithelium and epithelium undergo remodeling as an integrated unit, we performed morphological examination of 55 bronchial biopsy specimens obtained from explanted or resected lungs from tobacco smokers with COPD. Our results indicate that reticular basement membrane (RBM) thickness is increased and the subepithelial microvascular bed is reduced in association with progression from the normal epithelium to squamous metaplasia. Subsequent bronchial epithelial transformation to dysplasia is characterized by differential subepithelial remodeling with normalization of RBM thickness and subepithelial blood vessel density. Because fibrous remodeling of the subepithelium could limit delivery of nutrients and oxygen to the epithelium, we assessed expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CA IX) as markers of cellular hypoxia. The number of HIF-1alpha-positive epithelial cells increased with progression of epithelial structural changes, RBM thickness, and reduction in blood vessels in the subepithelium. These findings suggest that the HIF-1alpha pathway is activated in response to subepithelial remodeling and contributes to progressive premalignant epithelial lesions in the airways of tobacco smokers with chronic airway inflammation.
Asunto(s)
Bronquios/patología , Bronquios/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Mucosa Respiratoria/patología , Mucosa Respiratoria/fisiopatología , Adulto , Anciano , Antígenos de Neoplasias/metabolismo , Membrana Basal/metabolismo , Membrana Basal/patología , Membrana Basal/fisiopatología , Biopsia , Bronquios/metabolismo , Anhidrasa Carbónica IX , Anhidrasas Carbónicas/metabolismo , Hipoxia de la Célula/fisiología , Progresión de la Enfermedad , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Lesiones Precancerosas/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Mucosa Respiratoria/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Severe sepsis in lung transplant recipients is a challenging problem and carries a high mortality. Recombinant human activated protein C (drotrecogin alfa [activated]) has been approved for use in patients with severe sepsis. Its use has been shown to be safe and impart a survival advantage. However, the safety of drotrecogin alfa activated has not been evaluated in lung transplant recipients. We report for the first time on the use of drotrecogin alfa activated in six lung transplant recipients. Clinical trials are warranted to further evaluate the use of drotrecogin alfa activated in transplant recipients.
Asunto(s)
Trasplante de Pulmón , Proteína C/uso terapéutico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Many lung transplant programs employ lengthy regimens of IV ganciclovir therapy to prevent disease due to cytomegalovirus (CMV). In 1994, we introduced a regimen of delayed ganciclovir prophylaxis for CMV infection. This consisted of 2 weeks of IV ganciclovir therapy, initiated 3 to 4 weeks after transplantation, with subsequent viral monitoring and preemptive therapy as needed. When not receiving ganciclovir, patients received oral acyclovir, 800 mg tid, for 6 months. CMV-seronegative patients with seropositive donors also received four doses of CMV hyperimmune globulin. This study analyzes the CMV outcomes of 54 patients who received the delayed regimen compared to 33 historical control subjects who received only acyclovir prophylaxis (n = 28) or oral acyclovir and 2 to 4 weeks of ganciclovir early after transplantation (n = 5). METHODS: CMV detection was by shell vial culture or IgG seroconversion; after 1996, CMV detection was by blood antigenemia. The diagnosis of CMV disease also required a typical clinical syndrome or pathologic evidence of CMV. The main outcome was the actuarial incidence of CMV infection and disease. In order to account for the effect of other important risk factors for CMV infection, the time to CMV infection and disease was also studied as dependeant variables in a Cox proportional-hazard analysis, with the delayed regimen and other important risk factors as independent variables. RESULTS: The delayed regimen reduced the actuarial incidence of CMV infection from 80 to 48% (p < 0.001) and CMV disease from 31 to 10% (p < 0.01). No seropositive patient receiving the delayed regimen developed CMV disease. Twelve of the 54 patients in the study group required additional IV antiviral treatment, but the total use of ganciclovir averaged only 18 days per patient. In a Cox proportional-hazards model, the use of delayed ganciclovir was the only factor that showed a significant association with freedom from CMV infection (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.24 to 0.75; p = 0.003) and CMV disease (HR, 0.29; 95% CI, 0.10 to 0.86; p = 0.03). CONCLUSION: A regimen of CMV prophylaxis employing 2 weeks of IV ganciclovir initiated 3 to 4 weeks after lung transplantation followed by virologic monitoring and preemptive therapy as needed provides good protection against CMV disease.
Asunto(s)
Antivirales/administración & dosificación , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/administración & dosificación , Trasplante de Pulmón , Aciclovir/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Inmunoglobulina G/análisis , Inmunoglobulinas/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Fungal infections are an important complication of lung transplantation, but no controlled studies of their management have been performed. Knowledge of actual anti-fungal strategies may aid in the design of future prospective studies. METHODS: Thirty-seven of 69 active lung transplant centers, accounting for 66% of all US lung transplantations, responded to our survey. The survey focused on fungal surveillance, pre- and post-transplant prophylaxis, and approach to fungal colonization. RESULTS: The median number of lung transplantations performed by the centers in 1999 was 14 per year (range, 1-52), and median time that centers were in in operation was 9 years (range, 2-15 years). Seventy percent of centers had a transplant infectious diseases specialist. Pre-transplant fungal surveillance was performed by 81% of centers, with 67% of these surveying all patients and the remainder surveying only sub-sets of patients. Seventy-two percent of all centers started anti-fungal treatment if Aspergillus spp were isolated before transplantation. Itraconazole was the preferred agent (86%). After transplantation, 76% of centers gave anti-fungal prophylaxis, although 24% of these did so only in selected patients. Prophylactic agents in order of preference were inhaled amphotericin B (61%), itraconazole (46%), parenteral amphotericin formulations (25%), and fluconazole (21%); many centers used more than 1 agent. Prophylaxis was initiated within 24 hours by 71% and within 1 week by all centers. Median duration of prophylaxis was 3 months (range, <1 month-lifetime). All 37 centers used anti-fungal therapy if colonization with Aspergillus spp was detected for a median duration of 4.5 months. Itraconazole was the preferred agent. Only 59% of centers treated patients colonized with Candida spp. In a statistical analysis, centers with larger volumes were less likely to treat pre-transplant colonization with Candida spp but more likely to use agents other than itraconazole for post-transplant colonization with Aspergillus spp. Only 14% of centers engaged in any anti-fungal research at the time of the survey. CONCLUSIONS: The majority of surveyed lung transplant programs actively manage fungal infection with prophylaxis or pre-emptive therapy, despite the absence of controlled trials. This survey may provide an impetus and a basis for designing prospective studies.
Asunto(s)
Antifúngicos/uso terapéutico , Enfermedades Pulmonares Fúngicas/prevención & control , Trasplante de Pulmón , Infecciones Oportunistas/prevención & control , Premedicación , Anfotericina B/uso terapéutico , Aspergilosis/diagnóstico , Aspergilosis/prevención & control , Broncoscopía , Candidiasis/prevención & control , Encuestas de Atención de la Salud , Humanos , Itraconazol/uso terapéutico , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/tratamiento farmacológico , Estados UnidosRESUMEN
BACKGROUND: Low rates of major complications have been reported for the intussuscepting bronchial anastomotic technique but stenosis, malacia, and granulation tissue at the anastomosis may cause clinically important morbidity. We hypothesized that a modification of the telescoping technique that improves bronchial wall apposition might be associated with improved bronchial healing and clinical outcomes. METHODS: The telescoping horizontal mattress "U-stitch" suture technique was modified to incorporate figure-of-eight sutures placed in the cartilaginous wall between each of three intussuscepting U stitches. Serial videotape records of 152 individual anastomoses (99 modified, 53 telescoped) in 118 consecutive operative survivors were retrospectively reviewed by examiners blinded with respect to technique used. Stenosis, airway instability, mucosa quality, and devascularized luminal tissue were graded at 4 to 14 days (initial), 4 to 12 weeks (early), and 6 to 12 months (late) after transplantation. RESULTS: The incidence of anastomotic stenosis was significantly lower using the modified technique at the initial (p = 0.025) and late (p = 0.015) observations. In the initial phase airway instability (p = 0.015) and devascularization grades (p = 0.001) were also significant lower in the modified group. There were no significant differences in mucosal condition between techniques. The modified telescoping technique was associated with significant survival advantage (mean 17.7%; p = 0.029) by multivariate analysis. The incidence of major airway complications (dehiscences and stenoses required stents) tended to be lower (3% versus 6%) in the modified group. CONCLUSIONS: The modified telescoping bronchial anastomosis technique is associated with improved early and late bronchial healing and higher 5-year survival without increased major airway complications.
Asunto(s)
Anastomosis Quirúrgica/métodos , Bronquios/cirugía , Trasplante de Pulmón/métodos , Insuficiencia Respiratoria/cirugía , Enfermedades Bronquiales/etiología , Enfermedades Bronquiales/mortalidad , Enfermedades Bronquiales/prevención & control , Broncoscopía , Constricción Patológica/etiología , Constricción Patológica/mortalidad , Constricción Patológica/prevención & control , Estudios de Seguimiento , Humanos , Trasplante de Pulmón/mortalidad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Insuficiencia Respiratoria/mortalidad , Estudios Retrospectivos , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/mortalidad , Dehiscencia de la Herida Operatoria/prevención & control , Tasa de Supervivencia , Técnicas de Sutura , Resultado del TratamientoRESUMEN
BACKGROUND: Polyomavirus infection causes nephropathy after kidney transplantation but has not been thoroughly investigated in nonrenal organ transplantation. METHODS: Ninety lung transplant recipients were enrolled, and they provided urine samples for over 4.5 years. Samples were analyzed for BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) by conventional and quantitative real-time polymerase chain reaction. RESULTS: Fifty-nine (66%) patients had polyomavirus detected at least once, including 38 patients (42%) for BKV, 25 patients (28%) for JCV, and six patients (7%) for SV40. Frequency of virus shedding in serial urine samples by patients positive at least once varied significantly among viruses: JCV, 64%; BKV, 48%; and SV40, 14%. Urinary viral loads for BKV (10 copies/mL) and JCV (10 copies/mL) were higher than for SV40 (10 copies/mL; P=0.001 and 0.0003, respectively). Polyomavirus infection was associated with a pretransplant diagnosis of chronic obstructive pulmonary disease (odds ratio 6.0; P=0.016) but was less common in patients with a history of acute rejection (odds ratio 0.28; P=0.016). SV40 infection was associated with sirolimus-based immunosuppression (P=0.037). Reduced survival was noted for patients with BKV infection (P=0.03). Patients with polyomavirus infection did not have worse renal function than those without infection, but in patients with BKV infection, creatinine clearances were lower at times when viral shedding was detected (P=0.038). CONCLUSIONS: BKV and JCV were commonly detected in the urine of lung transplant recipients; SV40 was found at low frequency. No definite impact of polyomavirus infection on renal function was documented. BKV infection was associated with poorer survival.
Asunto(s)
Virus BK/aislamiento & purificación , Trasplante de Corazón-Pulmón/efectos adversos , Virus JC/aislamiento & purificación , Enfermedades Renales/virología , Trasplante de Pulmón/efectos adversos , Infecciones por Polyomavirus/virología , Virus 40 de los Simios/aislamiento & purificación , Adulto , Virus BK/genética , Biomarcadores/sangre , Creatinina/sangre , ADN Viral/orina , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Trasplante de Corazón-Pulmón/mortalidad , Humanos , Virus JC/genética , Estimación de Kaplan-Meier , Enfermedades Renales/mortalidad , Enfermedades Renales/fisiopatología , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Infecciones por Polyomavirus/complicaciones , Infecciones por Polyomavirus/mortalidad , Infecciones por Polyomavirus/fisiopatología , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Virus 40 de los Simios/genética , Factores de Tiempo , Orina/virología , Esparcimiento de VirusRESUMEN
BACKGROUND: From 1984 to 2006, studies of sleep in patients with interstitial lung disease revealed disturbed sleep, frequent nocturnal desaturations, nocturnal cough, and obstructive sleep apnea (OSA). Our goal was to analyze OSA in an outpatient population of stable patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients with IPF who had been followed up in the Vanderbilt Pulmonary Clinic were asked to participate. All patients were given a diagnosis of IPF by the 2000 American Thoracic Society consensus statement criteria. Subjects completed an Epworth sleepiness scale (ESS) questionnaire and a sleep apnea scale of sleep disorders questionnaire (SA-SDQ) before undergoing nocturnal polysomnography (NPSG). OSA was defined as an apnea-hypopnea index (AHI) of > 5 events per hour. RESULTS: Fifty subjects enrolled and completed a NPSG. The mean age was 64.9 years, and the mean BMI was 32.3. OSA was diagnosed in 88% of subjects. Ten subjects (20%) had mild OSA (AHI, 5 to 15 events per hour), and 34 subjects (68%) had moderate-to-severe OSA (AHI, > 15 events per hour). Only 6 subjects (12%) had a normal AHI. One patient was asymptomatic as determined by ESS and SA-SDQ, but had an AHI of 24 events per hour. The sensitivity of the ESS was 75% with a specificity of 15%, whereas the SA-SDQ had a sensitivity of 88% with a specificity of 50%. BMI did not correlate strongly with AHI (r = 0.30; p = 0.05). CONCLUSIONS: OSA is prevalent in patients with IPF and may be underrecognized by primary care providers and specialists. Neither ESS nor SA-SDQ alone or in combination was a strong screening tool. Given the high prevalence found in our sample, formal sleep evaluation and polysomnography should be considered in patients with IPF.
Asunto(s)
Fibrosis Pulmonar Idiopática/complicaciones , Apnea Obstructiva del Sueño/etiología , Anciano , Análisis de Varianza , Femenino , Humanos , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Persona de Mediana Edad , Polisomnografía , Prevalencia , Estudios Prospectivos , Pruebas de Función Respiratoria , Sensibilidad y Especificidad , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/fisiopatología , Encuestas y CuestionariosRESUMEN
Chronic bronchitis is a relatively common entity among patients with underlying chronic obstructive lung disease. Typical treatment includes pulmonary hygiene, bronchodilators, and antimicrobial therapy. In recent years, the duration of antimicrobial therapy in acute exacerbations of COPD has become shorter and shorter. This review summarizes the data on the use of the drug azithromycin for this particular patient population with a focus on 3-day and single-day therapy.
Asunto(s)
Antiinfecciosos/uso terapéutico , Azitromicina/uso terapéutico , Bronquitis Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Antiinfecciosos/administración & dosificación , Azitromicina/administración & dosificación , Bronquitis Crónica/etiología , Química Farmacéutica , Esquema de Medicación , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Recurrencia , Resultado del TratamientoRESUMEN
Chylous effusions are a well-described complication of lymphangioleiomyomatosis (LAM) in both pre- and post-transplant patients. Chylous effusions can cause significant morbidity among patients and most treatment modalities have limitations to complete success. We describe the use of a pleurovenous shunt to treat a refractory chylous effusion in a patient after lung transplant for LAM. After shunt placement, the patient had complete resolution of the chylous effusion and subsequent discharge home after a prolonged hospitalization. The use of a pleurovenous shunt for refractory chylous effusions is a viable option after conventional therapy fails.
Asunto(s)
Quilotórax/cirugía , Drenaje/métodos , Neoplasias Pulmonares/cirugía , Trasplante de Pulmón , Linfangioleiomiomatosis/cirugía , Pleura/cirugía , Complicaciones Posoperatorias , Vena Subclavia/cirugía , Adolescente , Quilotórax/etiología , Femenino , Humanos , Prótesis e ImplantesRESUMEN
BACKGROUND: Polyomavirus infection causes renal dysfunction after kidney transplantation, but it has not been thoroughly investigated in nonrenal solid-organ transplantation. METHODS: Fifty lung-transplant recipients provided prospective urine and blood samples over the course of 17 months. Samples were analyzed for BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) using conventional polymerase chain reaction (PCR), sequence analysis, and quantitative real-time PCR. RESULTS: Thirty-one (62%) of 50 patients had polyomavirus detected in at least 1 urine specimen, including 16 (32%) for BKV, 12 (24%) for JCV, and 6 (12%) for SV40. Mean BKV loads (5.0 log(10) copies/mL) did not differ from those of JCV (5.7 log(10) copies/mL; P=.38), but SV40 loads (2.5 log(10) copies/mL) were lower than those of BKV (P=.006) and JCV (P=.002). Blood samples were negative. Infection with individual polyomaviruses or polyomavirus infection in aggregate was not associated with reduced creatinine clearance. Patients not shedding polyomavirus had better survival than patients shedding polyomavirus (P=.049). CONCLUSIONS: Polyomaviruses BKV and JCV were commonly detected in urine from lung-transplant recipients. SV40 was found in 12% of patients but was shed at a lower frequency and with lower viral loads than the other viruses. Polyomavirus infection was not associated with renal dysfunction.
Asunto(s)
Trasplante de Pulmón , Infecciones por Polyomavirus/virología , Poliomavirus/aislamiento & purificación , Complicaciones Posoperatorias/virología , Infecciones Tumorales por Virus/virología , ADN Viral/sangre , ADN Viral/orina , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Poliomavirus/genética , Infecciones por Polyomavirus/sangre , Infecciones por Polyomavirus/orina , Estudios Prospectivos , Infecciones Tumorales por Virus/sangre , Infecciones Tumorales por Virus/orinaRESUMEN
Mediastinal fibrosis can present with a multitude of symptoms, most commonly cough, dyspnea and hemoptysis. We describe a case of mediastinal fibrosis secondary to histoplasmosis, which presented with both superior vena cava syndrome (SVCS) and hemoptysis. Our patient was successfully treated with bronchial artery embolization followed by SVC stent placement during a brief hospital stay.
Asunto(s)
Embolización Terapéutica , Hemoptisis/terapia , Enfermedades del Mediastino/terapia , Stents , Síndrome de la Vena Cava Superior/terapia , Angiografía , Enfermedad Crónica , Terapia Combinada , Diagnóstico Diferencial , Femenino , Fibrosis , Hemoptisis/diagnóstico por imagen , Hemoptisis/etiología , Histoplasmosis/complicaciones , Humanos , Enfermedades del Mediastino/complicaciones , Enfermedades del Mediastino/diagnóstico por imagen , Persona de Mediana Edad , Síndrome de la Vena Cava Superior/diagnóstico por imagen , Síndrome de la Vena Cava Superior/etiologíaRESUMEN
Chylothorax occurs when a disruption in the thoracic duct allows chyle to escape into the pleural space. The most commonly reported cause is malignancy, especially lymphoma. However, chylothorax caused by chronic lymphocytic leukemia is rarely reported in the literature. We describe a patient who developed chylothorax secondary to chronic lymphocytic leukemia. In addition, the pathogenesis, diagnosis, and treatment of chylothorax are reviewed.
Asunto(s)
Quilotórax/etiología , Leucemia Linfocítica Crónica de Células B/complicaciones , Anciano , Quilotórax/fisiopatología , Resultado Fatal , Humanos , Leucemia Linfocítica Crónica de Células B/fisiopatología , MasculinoRESUMEN
Adult respiratory distress syndrome (ARDS) and sepsis are known, life-threatening complications of miliary tuberculosis. This report describes a patient with miliary tuberculosis who rapidly developed an acute tuberculous empyema. She had a fulminant course culminating in ARDS, sepsis and subsequent death. This case highlights the rare association of acute empyema with miliary tuberculosis.
Asunto(s)
Empiema Tuberculoso/etiología , Tuberculosis Miliar/complicaciones , Enfermedad Aguda , Anciano , Comorbilidad , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/patología , Empiema Tuberculoso/epidemiología , Resultado Fatal , Femenino , Humanos , Insuficiencia Multiorgánica/etiología , Derrame Pleural/microbiología , Choque Séptico/etiología , Tuberculosis Miliar/epidemiología , Tuberculosis Miliar/patologíaRESUMEN
Antibody-mediated rejection is well established for renal allografts but remains controversial for lung allografts. Cardinal features of antibody-mediated rejection in renal allografts include antibodies to donor human leukocyte antigen (HLA) and evidence for antibody action, such as complement activation demonstrated by C4d deposition. We report a lung allograft recipient with circulating antibodies to donor HLA who failed treatment for acute cellular rejection but responded to therapy for humoral rejection. To address the second criteria for antibody-mediated rejection, we determined whether complement activation could be detected by measuring C4d in bronchoalveolar lavage fluid (BALF) by ELISA. Airway allergen challenge of asthmatics activates the complement pathway; therefore, we used BALF from asthmatics pre- and post-allergen challenge to measure C4d. These controls demonstrated that ELISA could detect increases in C4d after allergen challenge. BALF from the index patient had elevated C4d concomitant with graft dysfunction and anti-donor HLA in the absence of infection. Analysis of BALF from 25 additional lung allograft recipients showed that C4d concentrations >100 ng/mL were correlated with anti-HLA antibodies (p = 0.006), but were also observed with infection and in asyptomatic patients. The findings support the occurrence of anti-HLA-mediated lung allograft rejection and suggest that C4d measurement in BALF may be useful in diagnosis.