Showing papers on "Alveolar capillary dysplasia published in 2006"

Molecular Mechanisms of Pulmonary Vascular Development

Abstract: In this era of rapidly advancing vascular biology research, a vast array of growth factors and signaling molecules have been recognized as key players in the mechanisms that control lung vascular development. In the lung, vascular development is a complex, multistep process that includes specialization of primitive cells to vascular progenitors; formation of primitive vascular networks; remodeling with local regression and branching; specialization toward arteries, veins, and lymphatics; stabilization of vessels by matrix production and recruitment of supporting cells; and maintenance of the vascular structure. This complex, highly organized process requires exquisite orchestration of the regulatory activity of multiple molecules in a specific temporospatial order. Most of these molecules are members of 3 major growth factor families that have been recently identified. They are the vascular endothelial growth factor, angiopoietin, and ephrin families. Understanding the functional reach of several members of these growth factor families is integral to an appreciation of the etiology and pathogenesis of developmental lung vascular disorders affecting newborns. This review summarizes recent advances in the molecular bases of lung vascular development and some of the pulmonary diseases resulting from aberrant vascular growth, including bronchopulmonary dysplasia, alveolar capillary dysplasia, congenital cystic pulmonary disorders, congenital pulmonary hemangiomatosis, and lung hypoplasia.

Arteries and veins

Abstract: The lung's vasculature is different from that of most other organs because it has a double arterial supply and a double venous drainage system. The pulmonary artery which carries deoxygenated blood to the lungs branches alongside the airways into conventional and supernumerary arteries before it empties into the vast capillary network in the alveolar walls where gas exchange occurs across air–blood barriers. Conventional and supernumerary pulmonary veins drain oxygenated blood to the left atrium of the heart. The smaller (intra-acinar) vessels develop at the same time as do the acini of the lung and a major component of acinar lung development occurs postnatally. Alveoli increase from about 20 million at birth to about 300 million by the time lung growth is complete in adolescence. Consequently, a large component of intra-acinar vessels develop postnatally and during this critical growth phase are susceptible to local influences such as increased blood flow from intracardiac left to right shunts which can curtail vessel growth. Arterial wall structure is composed of endothelial cells that line the lumen, smooth muscle cells that make up the media, and fibroblasts that contribute the adventitial fibrous sheath. The wall structure changes from proximal to distal vessels in the lung, and alterations in the normal structure may occur during intrauterine life or postnatally in response to a variety of stimuli. Altered wall structure results in functional changes reflected in pulmonary artery pressure and resistance. Blood vessel assembly begins in primitive mesenchymal cells that undergo a complex series of steps before the mature vessel structure and function is attained. These stages in vessel development are under the control of a large number of transcriptional and growth factors. The timing and dose of some of these ‘angiogenic’ factors is critical to normal embryonic and fetal development; absence or even reduced expression of some factors is lethal for the developing embryo.

Late presentation of alveolar capillary dysplasia in an infant.

Abstract: Objective: To report a case of late presentation of alveolar capillary dysplasia and misalignment of pulmonary veins. Design: Descriptive case report. Setting: Pediatric intensive care unit of a tertiary care children's hospital. Patient: Seven-week-old female infant with severe hypoxemic respiratory failure. Conclusion: Alveolar capillary dysplasia with misalignment of pulmonary veins is a cause of primary pulmonary hypertension in newborns that can rarely present past the newborn period. Early lung biopsy can be helpful in establishing the diagnosis and avoiding ineffective, futile, and expensive therapeutic interventions.

Capillary apposition and density in the diagnosis of alveolar capillary dysplasia

Abstract: Aim: Alveolar capillary dysplasia (ACD) is a rare disorder, typically presenting with persistent pulmonary hypertension of the newborn. The aim was to characterise further the histological features of patients suspected of having ACD and to correlate histopathological features with outcome. Methods and results: Three pathologists retrospectively reviewed 21 surgical lung biopsy specimens (SLBx) where ACD entered the differential diagnosis. Semi-quantitative assessment showed that there was a spectrum of muscular arterial hypertrophy, capillary apposition to epithelium and capillary density within the interstitium, with the latter being more disordered in ACD. Misalignment of pulmonary vessels was also frequently seen. Four of 19 patients survived beyond the neonatal period, these having higher degrees of capillary apposition and density. Associated extrapulmonary abnormalities were common, most frequently with ACD. Conclusion: Poor capillary apposition and density, allied with medial arterial hypertrophy and misalignment of pulmonary vessels are the strongest diagnostic features of ACD. Of the four patients alive, all had high capillary apposition and density, suggesting that these features may be of prognostic value. SLBx remains useful in such cases as it may help predict patients who survive the neonatal period and also identify patients with disorders that are not primarily vascular anomalies.

Misalignment of pulmonary vessels with alveolar capillary dysplasia: Association with atrioventricular septal defect and quadricuspid pulmonary valve

Abstract: Misalignment of pulmonary vessels (MPV) with alveolar capillary dysplasia (ACD) is a complex congenital vascular abnormality in newborn infants. This condition is often associated with persistent pulmonary hypertension, which leads to severe respiratory distress and finally to the death of the newborn. Here, two cases of MPV with ACD are reported that were associated with atrioventricular septal defects. Both cases showed a combination of a large atrial septal defect and a smaller subvalvular ventricular septal defect. In one newborn, the cardiac malformation was accompanied by a quadricuspid pulmonary valve. These cases emphasize the importance of considering MPV with ACD a possible cause for pulmonary hypertension in the newborn, especially when a concomitant atrioventricular septal defect could represent an alternative explanation for the pulmonary hypertension.

Alveolar Capillary Dysplasia in a Patient with Down's Syndrome.

Abstract: To the Editor, I read the case report on a trisomy 21 patient with associated alveolar capillary dysplasia (ACD) by Shehata and Abramowsky [1] with great interest. This association is unique because it has not been described in the English literature before. Based on the presented clinical and pathologic data, in my opinion, the diagnosis of alveolar capillary dysplasia deserves careful reexamination. The clinical presentation, according to the provided very brief clinical history, is atypical for ACD. The vast majority of patients with ACD present with severe persistent pulmonary hypertension of newborn with rapid progression to respiratory distress requiring medical intervention [2]. ACD is regarded as a fatal disease; death occurs usually within 1 month after birth [2]. In contrast, the patient lacked the characteristic pulmonary history, and there was no mention of the usual pulmonary support that ACD patients require (i.e., extracorporeal membrane oxygenation, nitric oxide treatment). The length of survival of this patient is unusually long (3 months) especially without the above-mentioned treatment modalities. Peculiarly, the cause of death was not pulmonary, but rather septicemia-induced multiorgan failure. Although 2 rare reports documented a prolonged survival in ACD patient (22 days and 101 days), these patients had extensive medical support. Most importantly, the pathologic features, as presented, do not convincingly prove that there was pulmonary involvement by ACD. Figure 2 was intended to illustrate the microscopic diagnostic features of ACD. Personally, I found Figure 2 inadequate to assess the number and location of capillaries in the alveolar septae. In this picture, the authors pointed out ‘‘an occasional capillary,’’ but they did not give a detailed description in the corresponding figure legend. After careful examination I was able to spot a number of areas with similar size and same features. In the discussion, the authors briefly mentioned that the prolonged survival of the patient might be due to patchy involvement of the lung by ACD. Since there was no assessment of how patchy the ACD was in the pathology findings, this statement is not substantiated. Despite its obvious significance, it remains unclear if ACD involved the entire lung or one lobe or was indeed patchy. Moreover, there was no discussion and/or description of typical pulmonary findings in Down’s syndrome (pulmonary hypoplasia with decreased alveolar complexity) [3]. Misalignment of veins alone is not diagnostic for ACD, as it can be part of other lung diseases [4,5]. Lastly, given the patient’s history of mechanical ventilation, one could speculate that the presence of large, thin-walled channels within the pulmonary bronchoarterial units presented on Figure 1 may not be veins, but dilated blood-filled lymphatics. Given the uniqueness of this case, I believe that a more complete description (both clinical and histologic) is warranted. I would like to see the histopathologic evaluation of ACD and its distribution throughout the entire lung, possibly using CD31 immunostaining to better assess the location and number of capillaries with comparison to an agematched control, as well as an immunostain with D2– 40 antibody to differentiate between lymphatics and veins.

[Alveolar capillary dysplasia as a cause of failure in treatment of a neonate with pulmonary persistent hypertension of the newborn - case report].

Abstract: A patient with severe persistent pulmonary hypertension of the newborn (PPHN) due to alveolar capillary dysplasia, congenital (ACD), is presented. In the treatment, apart from standard methods, high frequency oscillatory ventilation (HFOV), inhaled nitric oxide and activated C protein have been applied. In spite of treatment the patient died and post-mortem diagnosis was based on lung histopathology examination. ACD occurs very rarely and is a congenital disease. Diagnosis is by pulmonary tissue histopathology examination. Pathological structure of the lungs leads to severe dysfunction of gas exchange as well as increasing pulmonary hypertension. No effective treatment is known and all so far described cases have ended up with death. The described case and literature data lead the authors to the following conclusions: 1. in case of PPHN resistant to treatment, ACD diagnosis should be taken into consideration, 2. histopathological examination determines the diagnosis, 3. limited capabilities of diagnosis are the reason for applying non-standard and expensive treatment methods which so far are doomed to failure, 4. in case of a patient with severe, persistent pulmonary hypertension and unclear aetiology, not reacting to nitrous oxide treatment, a diagnostic lung biopsy should be considered.