Surfactant therapy improves pulmonary function in infants withPneumocystis carinii pneumonia and acquired immunodeficiency syndrome

Creery, W. David; Hashmi, Aijaz; Hutchison, James S.; Singh, Richa

doi:10.1002/(sici)1099-0496(199711)24:5<370::aid-ppul10>3.0.co;2-6

Cited by 25 publications

(8 citation statements)

References 11 publications

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“…Consistent with our findings of surfactant abnormalities during PCP, other studies have found that surfactant replacement therapy can improve pulmonary function during PCP (6,7,22). In addition to restoring critical components, exogenous surfactant may also benefit PCP patients by inhibiting T-cell-dependent inflammatory responses (5) and diminishing neutrophil function (53).…”

Section: Fig 3 Effect Of Cd8supporting

confidence: 90%

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

et al. 2001

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During Pneumocystis carinii pneumonia (PCP) in mice, the degree of pulmonary inflammation correlates directly with the severity of lung function deficits. Therefore, studies were undertaken to determine whether the host inflammatory response contributes to PCP-related respiratory impairment, at least in part, by disrupting the pulmonary surfactant system. Protein and phospholipid content and surfactant activity were measured in the lavage fluid of infected mice in either the absence or presence of an inflammatory response. At 9 weeks postinfection with P. carinii, nonreconstituted SCID mice exhibited no signs of pulmonary inflammation, respiratory impairment, or surfactant dysfunction. Lavage fluid obtained from these mice had protein/phospholipid (Pr/PL) ratios (64% ؎ 4.7%) and minimum surface tension values (4.0 ؎ 0.9 mN/m) similar to those of P. carinii-free control mice. However, when infected SCID mice were immunologically reconstituted, an intense inflammatory response ensued. Pr/PL ratios (218% ؎ 42%) and minimum surface tension values (27.2 ؎ 2.7 mN/m) of the lavage fluid were significantly elevated compared to those of the lavage fluid from infected, nonreconstituted mice (P < 0.05). To examine the specific role of CD8 ؉ T-cell-mediated inflammation in surfactant dysfunction during PCP, mice with defined T-cell populations were studied. P. carinii-infected, CD4 ؉ -depleted mice had elevated lavage fluid Pr/PL ratios (126% ؎ 20%) and elevated minimum surface tension values (16.3 ؎ 1.0 mN/m) compared to normal mice (P < 0.05). However, when infected mice were additionally depleted of CD8 ؉ cells, Pr/PL ratios were normal and surfactant activity was improved. These findings demonstrate that the surfactant pathology associated with PCP is related to the inflammatory process rather than being a direct effect of P. carinii. Moreover, CD8؉ lymphocytes are involved in the mechanism leading to surfactant dysfunction.Pneumocystis carinii pneumonia (PCP) is a life-threatening opportunistic infection of the immunocompromised host. The clinical hallmark of PCP at presentation is tachypnea and hypoxia. Few rales are present upon auscultation of the chest, and X ray shows a diffuse pattern of alveolar disease. The mechanism by which P. carinii produces this clinical picture is poorly understood. One possible contributor to the constellation of signs and symptoms of PCP is direct or indirect disruption of the pulmonary surfactant system. Surfactant is a macromolecular complex of various phospholipids and specific proteins that regulates surface tension at the air-liquid interface within the alveolus. Surfactant-mediated reduction and variation of surface tension stabilize alveolar inflation and deflation behavior and reduce the work of breathing. Loss of surfactant activity results in decreased lung compliance, atelectasis, and impaired gas exchange.There have been several experimental observations that suggest that P. carinii has the potential to cause physiological disruption of the surfactant system. Sheehan et al. ...

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Section: Fig 3 Effect Of Cd8supporting

confidence: 90%

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

et al. 2001

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“…Selective intrabronchial instillation of surfactant via a flexible bronchoscope in an adult patient with lobar Gram-negative pneumonia resulted in a small improvement in oxygenation [175]. Similar improvements have been seen in HIV-infected infants with P. carinii pneumonia [176,177] or pneumonia caused by Respiratory syncytial virus [178].…”

Section: Infectious and Suppurative Lung Diseasesmentioning

confidence: 89%

Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

Dai¹,

Guzman²,

Costabel³

1999

Eur Respir J

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“…Surfactant dysfunction has been noted in humans and animals suffering from PCP (Sheehan et al 1986;Escamilla et al 1992;Hoffman et al 1992;Aliouat et al 1998;Atochina et al 2000;Schmidt et al 2006), and surfactant therapy has shown therapeutic benefit in both patients and experimental animals (Eijking et al 1992;Creery et al 1997). Dramatic alterations in surfactant phospholipid and protein composition, as well as impairment of physiological surfactant function are associated with PCP.…”

Section: Pathogenesismentioning

confidence: 99%

Pneumocystis

Gigliotti

Limper

Wright

2014

Cold Spring Harbor Perspectives in Medicine

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Surfactant therapy improves pulmonary function in infants withPneumocystis carinii pneumonia and acquired immunodeficiency syndrome

Cited by 25 publications

References 11 publications

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

Pulmonary Inflammation Disrupts Surfactant Function duringPneumocystis cariniiPneumonia

Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

Pneumocystis

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