Inflammation of small airways in asthma☆☆☆★★★

Hamid, Qutayba; Song, Yunling; Kotsimbos, T.; Minshall, Eleanor; Bai, Tony R.; Hegele, Richard G.; Hogg, James C.

doi:10.1016/s0091-6749(97)70193-3

Cited by 500 publications

(373 citation statements)

References 29 publications

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“…The administration of soluble OVA, followed by aerosol challenge, resulted in focal areas of eosinophilic inflammation that tended to be near the periphery of the lung rather than centrally located and to resemble human lesions (41,42). This pattern of inflammatory cell infiltration differs from well-established protocols inducing disease in Ͻ2 wk using OVA precipitated in alum.…”

Section: Discussionmentioning

confidence: 78%

Long-Lived Th2 Memory in Experimental Allergic Asthma

Mojtabavi¹,

Dekan

Stingl³

et al. 2002

The Journal of Immunology

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Although life-long immunity against pathogens is beneficial, immunological memory responses directed against allergens are potentially harmful. Because there is a paucity of information about Th2 memory cells in allergic disease, we established a model of allergic asthma in BALB/c mice to explore the generation and maintenance of Th2 memory. We induced disease without the use of adjuvants, thus avoiding Ag depots, and found that unlike allergic asthma in mice immunized with adjuvant, immunizing with soluble and aerosol OVA resulted in pathological lung lesions resembling human disease. To test memory responses we allowed mice with acute disease to recover and then re-exposed them to aerosol OVA a second time. Over 400 days later these mice developed OVA-dependent eosinophilic lung inflammation, airway hyperresponsiveness, mucus hypersecretion, and IgE. Over 1 year after recuperating from acute disease, mice had persistent lymphocytic lung infiltrates, Ag-specific production of IL-4 and IL-5 from spleen and lung cells in vitro, and elevated IgG1. Moreover, when recuperated mice were briefly aerosol challenged, we detected early expression of Th2 cytokine RNA in lungs. Taken together, these data demonstrate the presence of long-lived Th2 memory cells in spleen and lungs involved in the generation of allergic asthma upon Ag re-exposure.

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Section: Discussionmentioning

confidence: 78%

Long-Lived Th2 Memory in Experimental Allergic Asthma

Mojtabavi¹,

Dekan

Stingl³

et al. 2002

The Journal of Immunology

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“…Asthma is a chronic inflammatory disease of the airways including the most peripheral ones. There is abundant evidence that inflammatory and functional abnormalities of the lung periphery occur in all stages of the disease from the mildest [10,11] to the most severe form [12,13]. Interestingly, a correlation between disease severity and the magnitude of small airway impairment has been documented [14].…”

Section: The Role Of Small Airways In Asthma: Old Concepts and New Chmentioning

confidence: 99%

“…It is now accepted that inflammation is present throughout the bronchial tree of asthmatics; this inflammatory process is characterized by the presence of activated T lymphocytes and activated eosinophils, increased mucus plugging obstructing the lumen, and smooth muscle hyperplasia [17]. In a study designed to evaluate the inflammatory changes of large and small airways on lung tissue obtained from surgical resections of asthmatic subjects, the number of activated eosinophils was significantly greater in the distal portion of the airways and in the context of the alveolar walls [11,18].…”

Section: Peripheral Airways Pathology: the Strength Of Evidencementioning

confidence: 99%

Assessing and accessing the small airways; implications for asthma management

Scichilone

Contoli

Paleari

et al. 2013

Pulmonary Pharmacology & Therapeutics

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a b s t r a c tDespite the wealth of experience in the management of asthma, the disease remains inadequately controlled in some patients, who face long-term respiratory impairment and disability. The disease has been characterised as an inflammatory condition affecting first the larger airways and eventually the smaller airways, but there is evidence that peripheral airway involvement defines a particular and more severe phenotype of asthma. For this reason, assessing functional and biological parameters reflective of small airways involvement is important prognostically. No assessment method is universally and directly representative of peripheral airway function, but the traditional spirometric tests, including vital capacity, residual volume and forced vital capacity, are somewhat correlated with this function; useful methods for further assessment include the single-breath nitrogen wash-out test, impulse oscillometry, nitrous oxide and exhaled breath concentrate measurements, as well as computed tomography to reflect air trapping and response to treatment. Formulation advancements have made for easier treatment access to the smaller airways, with the new extrafine formulations resulting in better asthma control compared with non-extrafine formulations.

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“…Since in health, the 178 convection-diffusion front is thought to be located within the pulmonary acinus, S acin was 179 proposed as a putative physiological marker of acinar airspace disease. However, the precise 180 location of the convection-diffusion front is heavily dependent upon the molar mass of the 181 inert tracer gas being used, with heavier gases such as sulphur hexafluoride (SF 6 ) probing 182 more distal regions of the pulmonary acinus than lighter gases such as N 2 [10]. Elevations in…”

mentioning

confidence: 99%

“…MBW was performed according to current guidelines [39] using the SF 6 wash-in method 246 described by Horsley et al [40]. SF 6 was chosen as the inert tracer gas due to its heavy molar 247 mass, and based upon previous simulation data from Dutrieue et …”

mentioning

confidence: 99%