Abnormal alveolar attachments with decreased elastic fiber content in distal lung in fatal asthma.

Abstract:

:Small airway disease is thought to contribute significantly to functional impairment caused by asthma. Functional evidence of airway-parenchyma uncoupling in asthma, such as loss of deep breath bronchodilator effect in bronchoconstrictive episodes and enhanced airway closure, has been previously demonstrated. Elastic fibers are essential to maintain adequate elastic recoil of the lungs. In this study, we hypothesized that alveolar attachments could be abnormal and that elastic fibers could be damaged in the distal lungs of patients with fatal asthma. For this purpose, we measured the number of abnormal alveolar attachments and quantified the content of elastic fibers in the adventitial layer of small airways and in the peribronchial and distal alveolar septa of 15 patients who died of asthma (FA) and 9 control subjects (CTRL). Our data (geometric mean [range]) showed an increased proportion of abnormal alveolar attachments per centimeter of basement membrane perimeter in fatal asthma (FA, 0.18 [0.03-4.00]; CTRL, 0.00 [0.00-0.12]; p < 0.001) and decreased elastic fiber content in the small airway adventitial layer (FA, 4.08 [2.22-11.46] microm; CTRL, 6.79 [5.62-10.0] microm; p = 0.01) and in the peribronchial alveoli (FA, 1.08 [0.46-1.91] microm; CTRL, 1.81 [1.22-1.74] microm; p = 0.003), but not in the distal alveoli. We propose that structural alterations at the peribronchiolar level might contribute to the pathogenesis of some functional abnormalities observed in patients with severe asthma.

authors

Mauad T,Silva LF,Santos MA,Grinberg L,Bernardi FD,Martins MA,Saldiva PH,Dolhnikoff M

doi

10.1164/rccm.200403-305OC

keywords:

subject

Has Abstract

pub_date

2004-10-15 00:00:00

pages

857-62

issue

8

eissn

1073-449X

issn

1535-4970

pii

200403-305OC

journal_volume

170

pub_type

杂志文章
  • Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sputum of patients with cystic fibrosis.

    abstract::A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic pr...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.152.2.7633740

    authors: Delacourt C,Le Bourgeois M,D'Ortho MP,Doit C,Scheinmann P,Navarro J,Harf A,Hartmann DJ,Lafuma C

    更新日期:1995-08-01 00:00:00

  • Oleic acid inhibits alveolar fluid reabsorption: a role in acute respiratory distress syndrome?

    abstract::Levels of oleic acid (OA) are elevated in plasma and bronchoalveolar lavage fluids of patients with acute respiratory distress syndrome (ARDS). OA is also widely used to provoke edema, by unknown mechanisms, in experimental models of ARDS. We investigated the impact of intravascularly applied OA on epithelial lining f...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200407-954OC

    authors: Vadász I,Morty RE,Kohstall MG,Olschewski A,Grimminger F,Seeger W,Ghofrani HA

    更新日期:2005-03-01 00:00:00

  • Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial.

    abstract::Rationale: Recent retrospective evidence suggests the efficacy of early norepinephrine administration during resuscitation; however, prospective data to support this assertion are scarce. Objectives: To conduct a phase II trial evaluating the hypothesis that early low-dose norepinephrine in adults with sepsis with hyp...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.1164/rccm.201806-1034OC

    authors: Permpikul C,Tongyoo S,Viarasilpa T,Trainarongsakul T,Chakorn T,Udompanturak S

    更新日期:2019-05-01 00:00:00

  • Early-life air pollution and asthma risk in minority children. The GALA II and SAGE II studies.

    abstract:RATIONALE:Air pollution is a known asthma trigger and has been associated with short-term asthma symptoms, airway inflammation, decreased lung function, and reduced response to asthma rescue medications. OBJECTIVES:To assess a causal relationship between air pollution and childhood asthma using data that address tempo...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,多中心研究

    doi:10.1164/rccm.201302-0264OC

    authors: Nishimura KK,Galanter JM,Roth LA,Oh SS,Thakur N,Nguyen EA,Thyne S,Farber HJ,Serebrisky D,Kumar R,Brigino-Buenaventura E,Davis A,LeNoir MA,Meade K,Rodriguez-Cintron W,Avila PC,Borrell LN,Bibbins-Domingo K,Rodriguez-San

    更新日期:2013-08-01 00:00:00

  • Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis.

    abstract:RATIONALE:The clinical management of idiopathic pulmonary fibrosis (IPF) remains a major challenge due to lack of effective drug therapy or accurate indicators for disease progression. Fibrocytes are circulating mesenchymal cell progenitors that are involved in tissue repair and fibrosis. OBJECTIVES:To test the hypoth...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200810-1534OC

    authors: Moeller A,Gilpin SE,Ask K,Cox G,Cook D,Gauldie J,Margetts PJ,Farkas L,Dobranowski J,Boylan C,O'Byrne PM,Strieter RM,Kolb M

    更新日期:2009-04-01 00:00:00

  • Pleural fluid transforming growth factor-beta1 correlates with pleural fibrosis in experimental empyema.

    abstract::Transforming growth factor-beta1 (TGF-beta1) is a growth factor that is implicated in fibrosis of many organs. The purpose of this study was to determine the sequential levels of TGF-beta1 in the pleural fluid of rabbits that had undergone empyema induction, as fibrosis of the pleural space develops. Thirty-seven rabb...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.2202043

    authors: Sasse SA,Jadus MR,Kukes GD

    更新日期:2003-09-15 00:00:00

  • Tomographic study of the inflection points of the pressure-volume curve in acute lung injury.

    abstract::The inflection points of the pressure-volume curve have been used for setting mechanical ventilation in patients with acute lung injury. However, the lung status at these points has never been specifically addressed. In 12 patients with early lung injury we traced both limbs of the pressure-volume curve by means of a ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200312-1644OC

    authors: Albaiceta GM,Taboada F,Parra D,Luyando LH,Calvo J,Menendez R,Otero J

    更新日期:2004-11-15 00:00:00

  • Impaired nuclear translocation of the glucocorticoid receptor in corticosteroid-insensitive airway smooth muscle in severe asthma.

    abstract:RATIONALE:Patients with severe asthma (SA) are less responsive to the beneficial effects of corticosteroid (CS) therapy, and relative CS insensitivity has been shown in airway smooth muscle cells (ASMC) from patients with SA. OBJECTIVES:We investigated whether there was a defect in the actions of the glucocorticoid re...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201402-0314OC

    authors: Chang PJ,Michaeloudes C,Zhu J,Shaikh N,Baker J,Chung KF,Bhavsar PK

    更新日期:2015-01-01 00:00:00

  • Importance of myeloid dendritic cells in persistent airway disease after repeated allergen exposure.

    abstract:RATIONALE:There is conflicting information about the development and resolution of airway inflammation and airway hyperresponsiveness (AHR) after repeated airway exposure to allergen in sensitized mice. METHODS:Sensitized BALB/c and C57BL/6 mice were exposed to repeated allergen challenge on 3, 7, or 11 occasions. Air...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200505-783OC

    authors: Koya T,Kodama T,Takeda K,Miyahara N,Yang ES,Taube C,Joetham A,Park JW,Dakhama A,Gelfand EW

    更新日期:2006-01-01 00:00:00

  • The effect of mode, inspiratory time, and positive end-expiratory pressure on partial liquid ventilation.

    abstract::Partial liquid ventilation (PLV) has been shown to be an effective means of improving oxygenation in the injured lung. However, little is known about how approach to ventilation during PLV affects gas exchange and pulmonary mechanics. We hypothesized that gas exchange and pulmonary mechanics would be best with positiv...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.159.4.9711021

    authors: Fujino Y,Kirmse M,Hess D,Kacmarek RM

    更新日期:1999-04-01 00:00:00

  • The bactericidal activity of moxifloxacin in patients with pulmonary tuberculosis.

    abstract::Patients in whom acid-fast bacilli smear-positive pulmonary tuberculosis was newly diagnosed were randomized to receive 400 mg moxifloxacin, 300 mg isonaizid, or 600 mg rifampin daily for 5 days. Sixteen-hour overnight sputa collections were made for the 2 days before and for 5 days of monotherapy. Bactericidal activi...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1164/rccm.200305-682OC

    authors: Gosling RD,Uiso LO,Sam NE,Bongard E,Kanduma EG,Nyindo M,Morris RW,Gillespie SH

    更新日期:2003-12-01 00:00:00

  • Atelectasis causes alveolar injury in nonatelectatic lung regions.

    abstract:RATIONALE:Many authors have suggested that the mechanism by which atelectasis contributes to injury is through the repetitive opening and closing of distal airways in lung regions that are atelectatic. However, neither the topographic nor mechanistic relationships between atelectasis and distribution of lung injury are...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200506-1006OC

    authors: Tsuchida S,Engelberts D,Peltekova V,Hopkins N,Frndova H,Babyn P,McKerlie C,Post M,McLoughlin P,Kavanagh BP

    更新日期:2006-08-01 00:00:00

  • Impact of methicillin resistance on outcome of Staphylococcus aureus ventilator-associated pneumonia.

    abstract::The impact of methicillin resistance on morbidity and mortality of patients suffering from severe Staphylococcus aureus infections remains highly controversial. We analyzed a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant Staphylococcus aureus ventilator-ass...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200403-346OC

    authors: Combes A,Luyt CE,Fagon JY,Wollf M,Trouillet JL,Gibert C,Chastre J,PNEUMA Trial Group.

    更新日期:2004-10-01 00:00:00

  • Lung toxicity associated with cyclophosphamide use. Two distinct patterns.

    abstract::Cyclophosphamide-induced lung toxicity may be difficult to recognize because of the presence of confounding variables such as concomitant use of other cytotoxic drugs, opportunistic infections, diffuse pulmonary malignancy, radiation pneumonitis, and oxygen toxicity. The purpose of this retrospective analysis was to i...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1164/ajrccm.154.6.8970380

    authors: Malik SW,Myers JL,DeRemee RA,Specks U

    更新日期:1996-12-01 00:00:00

  • Cycle ergometer and inspiratory muscle training in chronic obstructive pulmonary disease.

    abstract::In patients with chronic obstructive pulmonary disease (COPD) the intensity of aerobic training is limited by dyspnea. Improving strength of the inspiratory muscles could enhance aerobic exercise training by reducing exercise-related dyspnea. We examined effects of home-based inspiratory muscle training (IMT) and cycl...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1164/ajrccm.160.2.9804067

    authors: Larson JL,Covey MK,Wirtz SE,Berry JK,Alex CG,Langbein WE,Edwards L

    更新日期:1999-08-01 00:00:00

  • Exhaled and nasal nitric oxide as a marker of pneumonia in ventilated patients.

    abstract::Because inflammation stimulates the expression of inducible nitric oxide (NO) synthase (iNOS) with an associated increased local NO production, we hypothesized that patients with pneumonia would have increased excretion of NO into their airways. To test this hypothesis, NO was measured in the exhaled air and from the ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.163.5.9906049

    authors: Adrie C,Monchi M,Dinh-Xuan AT,Dall'Ava-Santucci J,Dhainaut JF,Pinsky MR

    更新日期:2001-04-01 00:00:00

  • Persistent airway inflammation but accommodated antioxidant and lung function responses after repeated daily exposure to nitrogen dioxide.

    abstract::Nitrogen dioxide (NO2) is a common indoor and outdoor air pollutant that may induce deterioration of respiratory health. In this study the effects of repeated daily exposure to NO2 on airway antioxidant status, inflammatory cell and mediator responses, and lung function were examined. Healthy nonsmoking subjects were ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章

    doi:10.1164/ajrccm.159.2.9711068

    authors: Blomberg A,Krishna MT,Helleday R,Söderberg M,Ledin MC,Kelly FJ,Frew AJ,Holgate ST,Sandström T

    更新日期:1999-02-01 00:00:00

  • Purinergic receptor type 6 contributes to airway inflammation and remodeling in experimental allergic airway inflammation.

    abstract:RATIONALE:Extracellular nucleotides have recently been identified as proinflammatory mediators involved in asthma pathogenesis by signaling via purinergic receptors, but the role of the purinergic receptor type 6 (P2Y6R) has not been previously investigated. OBJECTIVES:To investigate the role of P2Y6R in asthma pathog...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201011-1762OC

    authors: Vieira RP,Müller T,Grimm M,von Gernler V,Vetter B,Dürk T,Cicko S,Ayata CK,Sorichter S,Robaye B,Zeiser R,Ferrari D,Kirschbaum A,Zissel G,Virchow JC,Boeynaems JM,Idzko M

    更新日期:2011-07-15 00:00:00

  • Human metapneumovirus in lung transplant recipients and comparison to respiratory syncytial virus.

    abstract:RATIONALE:Human metapneumovirus is a newly described virus isolated in 2001 from children with acute respiratory viral infection. It has subsequently been reported globally, although there are limited data in lung transplant recipients. OBJECTIVES:To prospectively analyze whether human metapneumovirus was circulating ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200711-1657OC

    authors: Hopkins P,McNeil K,Kermeen F,Musk M,McQueen E,Mackay I,Sloots T,Nissen M

    更新日期:2008-10-15 00:00:00

  • Future Research Directions in Asthma. An NHLBI Working Group Report.

    abstract::Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the N...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1164/rccm.201505-0963WS

    authors: Levy BD,Noel PJ,Freemer MM,Cloutier MM,Georas SN,Jarjour NN,Ober C,Woodruff PG,Barnes KC,Bender BG,Camargo CA Jr,Chupp GL,Denlinger LC,Fahy JV,Fitzpatrick AM,Fuhlbrigge A,Gaston BM,Hartert TV,Kolls JK,Lynch SV,Moo

    更新日期:2015-12-01 00:00:00

  • Tracheal gas insufflation: catheter effectiveness determined by expiratory flush volume.

    abstract::Used adjunctively during mechanical ventilation, tracheal gas insufflation (TGI) improves CO2 elimination, principally by decreasing effective anatomic dead space. Continuing lung deflation at end- expiration raises the end-expiratory C02 concentration within the proximal airway, and could theoretically reduce the eff...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.153.6.8665040

    authors: Ravenscraft SA,Shapiro RS,Nahum A,Burke WC,Adams AB,Nakos G,Marini JJ

    更新日期:1996-06-01 00:00:00

  • Bronchoalveolar lavage alterations in pulmonary embolism.

    abstract::The objective of this study was to determine quantitative and qualitative surfactant alterations, proteins, and platelet activating factor (PAF) in bronchoalveolar lavage (BAL) fluid from patients with pulmonary thromboembolism (PTE) with respect to ventilated patients without PTE. Patients with PTE underwent BAL at t...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.158.5.9802036

    authors: Nakos G,Kitsiouli EI,Lekka ME

    更新日期:1998-11-01 00:00:00

  • Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis.

    abstract:RATIONALE:Sepsis refers to the clinical syndrome of severe systemic inflammation precipitated by infection. Despite appropriate antimicrobial therapy, sepsis-related morbidity and mortality remain intractable problems in critically ill patients. Moreover, there is no specific treatment strategy for the syndrome of seps...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201001-0010OC

    authors: Mei SH,Haitsma JJ,Dos Santos CC,Deng Y,Lai PF,Slutsky AS,Liles WC,Stewart DJ

    更新日期:2010-10-15 00:00:00

  • Tumor necrosis factor-alpha -308 promoter gene polymorphism and increased tumor necrosis factor serum bioactivity in farmer's lung patients.

    abstract::Hypersensitivity pneumonitis (HP) represents an immunologic reaction of the pulmonary parenchyma to an inhaled agent. Since tumor necrosis factor (TNF)-alpha is thought to be involved in the pathogenesis of HP, and polymorphisms in the TNF genes have been associated with variations in the production of TNF-alpha, we i...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.163.2.2002062

    authors: Schaaf BM,Seitzer U,Pravica V,Aries SP,Zabel P

    更新日期:2001-02-01 00:00:00

  • Epithelial Na(+) channel (ENaC) expression in the developing normal and abnormal human perinatal lung.

    abstract::Impaired lung epithelial Na(+) channel (ENaC) activity at the time of birth results in respiratory distress. To investigate potential mechanisms, the ontogeny and cellular distribution of the alphaENaC subunit mRNA expression was studied in normal, immature, and abnormal (hypoplastic) human fetal lungs using nonradioi...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.161.4.9905064

    authors: Smith DE,Otulakowski G,Yeger H,Post M,Cutz E,O'Brodovich HM

    更新日期:2000-04-01 00:00:00

  • CD4 T Lymphocyte-mediated lung disease: steady state between pathological and tolerogenic immune reactions.

    abstract::Although considerable evidence indicates a role for CD4(+) T lymphocytes (T cells) in airway inflammation, little data exist regarding the mechanisms underlying the induction and regulation of CD4(+) T cell reactivity to lung-specific antigens. To dissect the immunologic and molecular mechanisms of CD4(+) T cell dysre...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200404-464OC

    authors: Bruder D,Westendorf AM,Geffers R,Gruber AD,Gereke M,Enelow RI,Buer J

    更新日期:2004-12-01 00:00:00

  • Outcomes after lung retransplantation in the modern era.

    abstract:RATIONALE:Characteristics of and survival estimates for recipients of lung retransplantation in the modern era are unknown. OBJECTIVES:To compare lung retransplant patients in the modern era with historical retransplant patients, to compare retransplant patients with initial transplant patients in the modern era, and ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200707-1132OC

    authors: Kawut SM,Lederer DJ,Keshavjee S,Wilt JS,Daly T,D'Ovidio F,Sonett JR,Arcasoy SM,Barr ML

    更新日期:2008-01-01 00:00:00

  • High incidence of posttransplant lymphoproliferative disease in pediatric patients with cystic fibrosis.

    abstract::A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk fa...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.161.4.9901013

    authors: Cohen AH,Sweet SC,Mendeloff E,Mallory GB Jr,Huddleston CB,Kraus M,Kelly M,Hayashi R,DeBaun MR

    更新日期:2000-04-01 00:00:00

  • Nocturnal Oximetry-based Evaluation of Habitually Snoring Children.

    abstract:RATIONALE:The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and glo...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201705-0930OC

    authors: Hornero R,Kheirandish-Gozal L,Gutiérrez-Tobal GC,Philby MF,Alonso-Álvarez ML,Álvarez D,Dayyat EA,Xu Z,Huang YS,Tamae Kakazu M,Li AM,Van Eyck A,Brockmann PE,Ehsan Z,Simakajornboon N,Kaditis AG,Vaquerizo-Villar F,Crespo S

    更新日期:2017-12-15 00:00:00

  • Future directions in sarcoidosis research: summary of an NHLBI working group.

    abstract::Sarcoidosis is a systemic granulomatous disease of unknown etiology that primarily affects the lungs. The etiology remains unclear; however, environmental, genetic, ethnic, and familial factors probably modify expression of the disease. As an example, African Americans are at greater risk of mortality and morbidity th...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1164/rccm.200308-1073WS

    authors: Martin WJ 2nd,Iannuzzi MC,Gail DB,Peavy HH

    更新日期:2004-09-01 00:00:00