Congenital cystic adenomatoid malformation of the lung: Hazards of delayed diagnosis

Congenital cystic adenomatoid malformation is a rare pulmonary developmental anomaly, which typically manifests in neonates and infants. Presentation in adulthood is uncommon, with <60 cases reported in the literature. The majority of cases involve one lobe only. We report a case of type 1 congenital cystic adenomatoid malformation in an adult presenting with a respiratory tract infection and haemoptysis. At thoracotomy, complex cystic masses were noted in the right upper and lower lobes. Lung-sparing surgery, in the form of two segmentectomies and a non-anatomical resection, was performed in order to avoid pneumonectomy. Such presentations may be problematic as potentially incomplete resections may increase the risk of complications and malignant transformation. This suggests the importance of appropriate clinical and radiological follow up.     

The glandular component in congenital cystic adenomatoid malformation of the lung

Although severe congenital cystic changes (CCC) of the lung may be fatal, less severe forms may regress or vanish spontaneously. With recent advances in sonography, asymptomatic CCC are increasingly found. Whether all CCC should be promptly excised, or not, is uncertain. Congenital cystic changes conceptually are bronchopulmonary foregut malformations (BPFM) with a predilection for malignant degeneration. Among all BPFM, congenital cystic adenomatoid malformation (CCAM) is most common. We therefore searched for evidence of early malignant transformation in five surgically excised and three autopsy lungs with CCAM. By light microscopy, CCAM resembled poorly formed and dilated bronchi, bronchioles and respiratory air spaces. Four lungs had multiple nodular aggregates of mucus producing cells; the glandular component (GC). By scanning electron microscopy, GC appeared as multiple micropolyps, resembling neuroepithelial bodies. By transmission electron microscopy, GC had a surface proliferation of cells with granules of the mucous type and a basal increase in cells with owl-eyed neuroendocrine granules. The glandular component in CCAM appeared similar to the mucous cells in hyperplastic polyps of the colon and a type of mucus producing bronchioloalveolar carcinoma. Our findings support the hypothesis that CCAM is caused by dysregulated paracrine growth of mature cells and extracellular matrices and that GC could have the potential for malignant transformation. Further clinical and laboratory studies of BPFM are needed for the appropriate management of congenital cystic changes.     

Rate of surfactant administration influences lung function and gas exchange in a surfactant-deficient rabbit model

The aim of this study was to test whether the effect of surfactant treatment on lung function in a surfactant-deficient animal model can be influenced by the rate at which surfactant is administered. Surfactant deficiency was induced in 18 New Zealand white rabbits (weighing approx. 1 kg each) by lung lavage with normal saline. The arterial/alveolar oxygen ratio (a/A ratio), functional residual capacity (FRC), dynamic compliance of the respiratory system (C_rs), tidal volume (V_T), alveolar portion of the tidal volume (V_A) and arterial PCO₂ (Pa,CO₂) were measured before and after lavage and 15, 30, 60, 90, and 120 min after administration of a single dose of surfactant (Survanta®, 100 mg/kg). Two surfactant administration protocols were compared over a 2-h interval: an infusion lasting 4 min and an infusion over 2 min. Both administrations were given during continuous mechanical ventilation. The six lung function and gas exchange parameters improved significantly following surfactant administration over 2 min compared with a control group. However, only the a/A ratio and V_A improved following the 4-min protocol. Comparison of the two intervention protocols yielded significantly differences in V_A and Pa,CO₂, favoring the shorter administration. These results support the hypothesis that fast (2 min) administration of surfactant will improve its distribution to formerly collapsed alveoli and results in better lung function, improved ventilation, and (to a lesser extent) better oxygenation than prolonged infusions (4 min). Pediatr. Pulmonol. 1998; 25:196–204. © 1998 Wiley-Liss, Inc.     

肺超声评分在新生儿呼吸窘迫综合征的诊断及预后评估应用

目的 分析肺超声评分在新生儿呼吸窘迫综合征(NRDS)诊断及预后的预测作用.方法 选取NRDS患儿145例,为NRDS组.另选取同期出生的无呼吸系统疾病新生儿150例为对照组.NRDS患儿根据出院时临床结局分为预后良好组与预后不良组,比较两组的肺部超声评分及其他可能影响预后的相关因素.Logistic回归分析明确NRD...     

Intrapulmonary application of a 5-lipoxygenase inhibitor using surfactant as a carrier reduces lung edema in a piglet model of airway lavage

Leukotriene-generated effects on microvascular integrity and polymorphonuclear leukocytes (PMNL) play a key role in the inflammatory process of the alveolar-capillary unit in neonatal acute respiratory distress syndrome. We asked if intrapulmonary application of MK886, a 5-lipoxygenase inhibitor, and the use of a porcine surfactant preparation (Curosurftrade mark) as a carrier substance would improve lung function in a neonatal piglet model of airway lavage. Anesthetized, mechanically ventilated newborn piglets (n = 19) underwent repeated airway lavage to induce acute lung injury. Piglets then received either surfactant alone (S, n = 6), or MK886 admixed with surfactant (S + MK, n = 7), or an air-bolus injection as control (C, n = 6). Measurements of gas exchange, lung function, extravascular lung water (EVLW), cell counts, and leukotriene B(4) (LTB(4)) concentrations in bronchoalveolar lavage fluid (BAL) were performed during 6 hr of mechanical ventilation. Arterial oxygen partial pressure (PaO(2)) (S, 13.8 +/- 4.2 kPa, vs. S + MK, 20 +/- 6.6; P < 0.05), functional residual capacity (S, 15.1 +/- 6.8 ml/kg, vs. S + MK, 18.8 +/- 3.7 ml/kg; P < 0.05), and EVLW (S, 29 +/- 14 ml/kg, vs. S + MK 24 +/- 4 ml/kg; P < 0.05) were significantly improved in the MK886 group. This clinical effect was linked with a decrease in LTB(4) concentration in BAL (S, 3.5 (1.9-5.4) pg/ml, vs. S + MK, 1.6 (0.7-4.7) pg/ml; P < 0.05) and an increase in IL-8 (S, 2,103 (852-4,243) pg/ml, vs. S + MK, 3,815 (940-26,187) pg/ml; P < 0.05). PMNL counts in BAL were reduced (S, 570 +/- 42 cells/ml, vs. 275 +/- 35 cells/ml; P < 0.05). In conclusion, intrapulmonary application of the 5-lipoxygenase inhibitor MK886 with surfactant as a carrier improves lung function by decreasing EVLW as the main response to LTB(4) reduction.     

Neutrophil transmigration triggers repair of the lung epithelium via beta-catenin signaling

Injury to the epithelium is integral to the pathogenesis of many inflammatory lung diseases, and epithelial repair is a critical determinant of clinical outcome. However, the signaling pathways regulating such repair are incompletely understood. We used in vitro and in vivo models to define these pathways. Human neutrophils were induced to transmigrate across monolayers of human lung epithelial cells in the physiological basolateral-to-apical direction. This allowed study of the neutrophil contribution not only to the initial epithelial injury, but also to its repair, as manifested by restoration of transepithelial resistance and reepithelialization of the denuded epithelium. Microarray analysis of epithelial gene expression revealed that neutrophil transmigration activated β-catenin signaling, and this was verified by real-time PCR, nuclear translocation of β-catenin, and TOPFlash reporter activity. Leukocyte elastase, likely via cleavage of E-cadherin, was required for activation of β-catenin signaling in response to neutrophil transmigration. Knockdown of β-catenin using shRNA delayed epithelial repair. In mice treated with intratracheal LPS or keratinocyte chemokine, neutrophil emigration resulted in activation of β-catenin signaling in alveolar type II epithelial cells, as demonstrated by cyclin D1 expression and/or reporter activity in TOPGAL mice. Attenuation of β-catenin signaling by IQ-1 inhibited alveolar type II epithelial cell proliferation in response to neutrophil migration induced by intratracheal keratinocyte chemokine. We conclude that β-catenin signaling is activated in lung epithelial cells during neutrophil transmigration, likely via elastase-mediated cleavage of E-cadherin, and regulates epithelial repair. This pathway represents a potential therapeutic target to accelerate physiological recovery in inflammatory lung diseases.     

Application of ultrasound in a congenital cystic adenomatoid malformation in an adult: A case report

Introduction:Congenital cystic adenomatoid malformation (CCAM) is a rare developmental lung abnormality, that typically manifests in neonates and infants but rarely in adults. Ultrasound is an important method of diagnosing CCAM in neonates and infants; however, few articles have reported the value of transthoracic lung ultrasound in the diagnosis of CCAM in adults.Patient concerns:We present a case of a 34-year-old woman with a cavitary lesion in her left lower lobe, that suggested chronic inflammation.Diagnosis:The patient underwent ultrasound examination and contrast-enhanced ultrasound-guided transthoracic core biopsy; histology suggested the diagnosis of lung hamartoma. Surgical resection of the lesion followed by histopathological analysis confirmed the diagnosis of CCAM.Interventions:The patient underwent transthoracic core biopsy under contrast-enhanced ultrasound guidance. A left lower lobectomy was then performed subsequently.Outcomes:The patient had a smooth recovery and remained asymptomatic during the 12-months of postoperative follow-up.Conclusion:We report a rare case of CCAM to suggest that transthoracic ultrasound combined with contrast-enhanced ultrasound is a safe and effective method of diagnosing the subpleural lung malformations in adults, thereby avoiding multiple radiation exposures and associated complications.     

Congenital lung disease: a plea for clear thinking and clear nomenclature

Antenatal ultrasound has allowed the discovery of abnormalities which in the past often escaped detection. It may be unclear what advice to offer. Many large lung malformations seen at the routine 20-weeks gestation scan have largely disappeared at term. There is now even more confusion in terms of how these malformations should be described. The nomenclature of congenital lung disease was never very clear, with terms such as sequestrated segment, cystic adenomatoid malformation, hypoplastic lung, and malinosculation being used to describe often overlapping abnormalities. However, today these terms are used inconsistently in the ante- and postnatal periods. For example, congenital cystic adenomatoid malformation (CCAM) is used prenatally to describe a lesion which may well disappear before birth, but is used postnatally to describe an abnormality which may require lobectomy. CCAM may have a pulmonary arterial supply, or be supplied like a sequestration from the aorta, and histological features of both lesions may coexist. Thus, a complete reappraisal of the nomenclature of congenital lung disease is timely; this review does not discuss treatment options.     

Effect of neonatal surfactant therapy on lung function at school age in children born very preterm

Our aim was to evaluate long-term effects of exogenous surfactant therapy on pulmonary functional outcome in children born very preterm. We examined 40 children aged 7–12 years who were born before 30 weeks of gestation with an immature surfactant system, and were randomized to one of three treatment groups: human surfactant given at birth (prophylactic), human surfactant given after development of neonatal respiratory distress syndrome (rescue), and placebo (air) treatment. Spirometric parameters of preterm born children were compared with those of 20 children born at term. In addition, spirometric parameters were monitored twice daily for 4 weeks using a home spirometer. All spirometric parameters were significantly lower in the preterm groups than in the controls, except for the forced vital capacity (FVC) in the prophylactically treated group. Bronchial obstruction was found in 53% of the prophylactically treated group, in 36% of the rescue group, in 67% of the placebo group, and in 0% of the control group. Peak expiratory flow (PEF) and FVC values were higher in those children who received surfactant compared with the placebo group (P < 0.05). In 16 children (40%) born preterm, a β₂-agonist induced an increase in PEF ≥15% at least three times during 2 weeks of home monitoring; eight children (20%) had abnormal diurnal PEF variation. Multiple regression analysis indicated that the independent variables associated with favorable outcomes in spirometric parameters were surfactant therapy (P = 0.012–0.045) and short intubation time after birth (P = 0.0009–0.0044). Bronchial obstruction, responsiveness to a β₂-agonist, and high diurnal PEF variation are common in children born before 30 gestational weeks. Surfactant supplementation reducing the need for mechanical ventilation or supplementary oxygen after birth may decrease the severity of immaturity related bronchial obstruction in childhood. Pediatr. Pulmonol. 1998; 25:182–190. © 1998 Wiley-Liss, Inc.     

Diffuse pulmonary ossification as a rare cause of interstitial lung disease

Diffuse pulmonary ossification (DPO) is a rare form of interstitial lung disease. The present article describes a case of DPO in an elderly man who presented with progressive dyspnea on exertion and an isolated reduction in diffusing capacity for carbon monoxide. DPO may occur as sequelae of mitral stenosis, left heart failure, idiopathic pulmonary fibrosis, recurrent aspiration pneumonia, solid organ transplant, adult respiratory distress syndrome or may arise idiopathically. In the absence of other findings of interstitial lung disease, a lung biopsy is unlikely to be helpful in the management of these patients.     

Sleep,respiratory rate,and growth hormone in chronic neonatal lung disease

This study assessed whether respiratory rates (RRs) correlate with urinary growth hormone (U-GH) excretion and sleep architecture in infants with chronic neonatal lung disease (CNLD) in early (1 month), middle (6 months), and late (10 months) infancy. Twenty-three preterm infants (CNLD = 16, controls = 7) were studied on 51 occasions. CNLD infants were stratified according to mean non-REM sleep respiratory rate (NREM RR) in early infancy into “High RR CNLD” infants (mean NREM RR >2 SD higher than controls) and “Normal RR CNLD” infants (mean NREM RR within 2 SD of controls' mean). “High RR CNLD” infants (RR >45) had a lower mean birthweight (P = 0.015), current weight (P = 0.042), current length (P = 0.02), and growth velocity in early infancy (grams/week gained: P = 0.042) than “Normal RR CNLD” and control infants. Mean (95% CI) U-GH excretion (ng U-GH/g urinary creatinine) was higher in “High RR CNLD” infants in air or their usual O₂ (1,932 [459, 3,406]) than “Normal RR CNLD” (394 [147, 642]) and controls (320 [147, 492]) (P = 0.024). With resolution of tachypnea by mid-infancy, hemoglobin oxygen saturation (SaO₂) >93%, mean growth parameters and U-GH excretion for the “High RR CNLD” group were not significantly different from “Normal RR CNLD” and control groups. CNLD infants demonstrated increased sleep efficiency (P = 0.016), whereas controls had similar sleep efficiency between early and middle infancy (P = 0.452). Mean percent time in REM sleep (REM%) and slow wave sleep (SWS%) were not significantly different between early and middle infancy and did not vary in relation to respiratory rate. We conclude that tachypneic infants with CNLD have slower growth and elevated U-GH excretion in early infancy. With resolution of tachypnea, growth improved, U-GH excretion decreased, and sleep consolidation occurred. An elevated U-GH in tachypneic CNLD infants may reflect stress, compromised nutrition (GH resistance), or a feedback loop involving a direct effect of GH on lung growth and repair. Pediatr Pulmonol. 1998; 26:241–249. © 1998 Wiley-Liss, Inc.     

Congenital cystic adenomatoid malformation of the lung in adults: clinical and CT evaluation of seven patients

Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare congenital developmental abnormality that usually presents in childhood. Some associated malignancies have been reported. This study aimed to describe the clinical and multidetector CT (MDCT) image characteristics of CCAM of the lung in adults. Adult patients with congenital cystic lung diseases in association with surgery for CCAM were evaluated over a five and a half year period. Seven (four women, age range 17-64 years) of 109 congenital cystic lung disease patients were histologically confirmed as having CCAM. The most frequent symptom was productive cough (n = 5) and one patient was admitted with haemoptysis. The diagnosis was based on clinical and radiological findings and one patient was not diagnosed until surgery. MDCT images consisted of having a multiple loculated unilobar cystic mass in six patients and a cavitary mass in one and/or normal systemic arteries. The lesion was present in the right lung in four and in the left lung in three patients. The involved lobe was the upper in three, lower in three and middle lobe in one. Six patients underwent lobectomy and there was no associated malignancy or mortality. The mean length of hospital stay was 17.5 +/- 7.3 days. In adult patients who suffer from a recurrent productive cough and who have a multiloculated cystic mass in one lobe and normal vascular images in MDCT, CCAM, although rare, should be considered.     

急性呼吸窘迫综合征时血管外肺水的检测方法及意义

急性呼吸窘迫综合征（ARDS）的本质是弥漫性肺泡毛细血管膜损伤、血管通透性增加所致的通透性肺水肿。血管外肺水（EVLW）的改变与肺水肿的程度具有高度相关性,EVLW作为预测、筛选ARDS患者以及反映ARDS患者病情、评价疗效和判断预后一个重要指标正在得到越来越广泛的的研究和使用。EVLW质和量的改变进行动态观察和定量检测,已成为呼吸窘迫综合综合征研究的热点,现就其检测方法和意义作一综述。