Late presentation of congenital diaphragmatic hernia in patients with cystic fibrosis

Late presentation of congenital diaphragmatic hernia (CDH) is unusual, especially in patients with cystic fibrosis (CF). To our knowledge, cases of CDH in CF patients and the combined effects on lung function have not been previously described. Here we report two cases of late presenting CDH in CF patients and describe effects on lung function. Late presentation of CDH in CF patients can cause gastrointestinal or respiratory symptoms and requires a high index of suspicion as well as proper interpretation of imaging. In patients with CF and CDH, lung function abnormalities could include obstructive, restrictive defects, or combined defects. Pediatr Pulmonol. 2010; 45:403–405. © 2010 Wiley‐Liss, Inc.     

Evolution of airway hyperresponsiveness in infants with severe congenital diaphragmatic hernia

Infants born with severe congenital diaphragmatic hernia (DH) characteristically have pulmonary hypoplasia. Airway hyperresponsiveness during the first 4 weeks of life can be demonstrated in most of these neonates. Early postnatal pulmonary development in infants with severe DH has not been well characterized. We examined lung growth in patients with congenital DH by using the forced deflation method to study pulmonary function in 18 infants on mechanical ventilation who survived neonatal repair of their congenital DH. Thirteen infants without primary pulmonary pathology who required general anesthesia for other surgery served as controls. Infants were further divided according to age at the time of testing into early (age ≤ 7 days at time of testing) and late (age ≥ 29 days) groups, yielding four groups of subjects: early diaphragmatic hernia (EDH): n = 9; mean age, 4.2 days, range, 1–7 days; early controls (EC): n = 8; mean age, 3.1 days; range, 1–6 days; late diaphragmatic hernia (LDH): n = 11; mean age, 57.7 days, range, 28–120 days; and late controls (LC); n = 5; mean age, 52.2 days; range 32–90 days. All infants were studied once, with the exception of two infants with DH who were studied on two occasions at EDH and LDH stages. A marked reduction in weight-corrected forced vital capacity (FVC) was seen in the EDH group (13.9 ± 3.9 ml/kg) as compared to the EC group (44.4 ± 4.9 ml/kg). During the ensuing 4 months of life, FVC in patients with LDH (24.5 ± 1.9 ml/kg) was much higher than FVC in patients with EDH (P < 0.05). These findings demonstrate the presence of pulmonary hypoplasia in the EDH group and suggest subsequent rapid postnatal lung growth. An index of rate, constant, MEF₂₅/FVC, as compared with control groups was abnormally elevated in EDH subjects (1.87 ± 0.30/second vs 1.16 ± 0.32/second, P < 0.05), indicating significantly increased lower airway caliber relative to lung volume. The severe reduction of the rate constant in the LDH group (0.36 ± 0.05/second vs 0.73 ± 0.07/second, P < 0.05) suggests the development of lower airway obstruction. After the administration of a nebulized bronchodilator (BD), an increase in MEF₂₅ (32.9%) in the EDH group was not significant, but an increase of 134.7% in the LDH group was significant (P < 0.05). Although the study utilized a cross-sectional design with most of the infants in either the early or late group, present findings suggest that infants with EDH have lung restriction reflecting pulmonary hypoplasia. These infants developed lower airway obstruction and airway hyperresponsiveness with only mild fixed obstruction over the first 4 months of life. Pediatr Pulmonol. 1996; 22:295–304. © 1996 Wiley-Liss, Inc.     

Developmental and genetic aspects of congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a frequent occurring cause of neonatal respiratory distress and occurs 1 in every 3,000 liveborns. Ventilatory support and pharmaceutical treatment of the co-occurring lung hypoplasia and pulmonary hypertension are insufficient in, respectively, 20% of isolated cases and 60% of complex ones leading to early perinatal death. The exact cause of CDH remains to be identified in the majority of human CDH patients and prognostic factors predicting treatment refraction are largely unknown. Their identification is hampered by the multifactorial and heterogenic nature of this congenital anomaly. However, application of high-resolution molecular cytogenetic techniques to patients' DNA now enables detection of chromosomal aberrations in 30% of the patients. Furthermore, recent insights in rodent embryogenesis pointed to a specific disruption of the early mesenchymal structures in the primordial diaphragm of CDH-induced offspring. Together, these data allowed for the introduction of new hypotheses on CDH pathogenesis, although many issues remain to be resolved. In this review, we have combined these new insights and remaining questions on diaphragm pathogenesis with a concise overview of the clinical, embryological, and genetic data available.     

Tension gastrothorax in late-onset congenital diaphragmatic hernia,a rare but life-threatening condition: A case report

Rationale:Tension gastrothorax is a serious condition that can cause acute respiratory failure, which is mostly related to congenital diaphragmatic hernia (CDH) in pediatric cases. It is uncommon in late-onset CDH patients, and is difficult to diagnose due to atypical presentation. It is often misdiagnosed as tension pneumothorax or pleural effusion, leading to delayed treatment and potentially fatal outcome. In this study, we are reporting our experience of diagnosis and treatment of tension gastrothorax in a late-onset CDH patient.Patient concerns:A 2-year old boy presented to this hospital with severe dyspnea and abdominal pain that suddenly occurred while taking a bath.Diagnosis:Based on radiological findings we diagnosed tension gastrothorax.Interventions:Hernia reduction and diaphragmatic defect repair were performed under thoracotomy.Outcomes:After the operation, the patient''s clinical symptoms and imaging findings improved. At 1-year postoperative follow up, the patient was well with normal chest x-ray findings.Lessons:Tension gastrothorax in late-onset CDH is a life-threatening condition that requires rapid diagnosis and treatment. When the diagnosis is unclear by chest x-ray, chest computed tomography should be performed to confirm the diagnosis. A nasogastric tube should be inserted whenever possible for diagnosis and gastric decompression. Although laparotomy is the most preferred approach, we recommend that surgeons consider taking a thoracotomy approach in unstable patients that cannot undergo gastric decompression before operation.     

Recurrence of a congenital diaphragmatic hernia 57 years postoperatively: A case report and review of the literature

Rationale:Postoperative recurrence of congenital diaphragmatic hernia (CDH) in adults is very rare. There is currently no precedent and no established treatment. We encountered a case of CDH which recurred 57 years, postoperatively.Patient concerns:A 57-year-old man with dyspnea on exertion was referred to our hospital. He had undergone surgery at the same hospital for CDH when he was 46 days old.Diagnosis and interventions:Laboratory studies, except diagnostic imaging and spirometry, were otherwise within normal limits. He was diagnosed with recurrent CDH based on computed tomography and underwent laparoscopic surgery.Outcomes:His postoperative course was uneventful, and there was no recurrence on follow-up.Lessons:We reported our encounter with a case of recurrent CDH, more than 50 years after the initial surgery. When managing diaphragmatic hernias, prompt surgical treatment, with consideration to prior surgical history for CDH, leads to satisfactory results.     

Congenital diaphragmatic hernia misdiagnosed as tension pneumothorax

Drainage of the pleural space is undertaken as an emergency when there is respiratory distress and the radiological appearance of mediastinal shift. We present two cases in which the initial diagnosis was tension pneumothorax and chest drains were inserted. In both cases, the diagnosis turned out to be congenital diaphragmatic hernia. Pediatr. Pulmonol. 1997;24:119–121. © 1997 Wiley-Liss, Inc.     

Lung volumes and distribution of ventilation in survivors to congenital diaphragmatic hernia (CDH) during infancy

The assessment of lung volumes, particularly functional residual capacity (FRC), is crucial for understanding lung development during infancy in CDH patients.AIM: To evaluate changes in lung function during infancy in subjects with CDH treated with a "gentle ventilation" technique and delayed surgery strategy in the neonatal period. METHODS: 13 CDH infants were studied twice and compared with a population of 28 healthy infants (HI). Tidal-Volume (Vt), respiratory rate (RR) and time to peak expiratory flow/expiratory time ratio (tPTEF/Te) were measured with an ultrasonic flow meter; Compliance (Crs) and Resistance (Rrs) of the respiratory system were studied with the single occlusion technique; FRC and Lung Clearance Index (LCI), were assessed with the sulfur hexafluoride (SF6) wash-in/wash-out technique. The differences between the first (T1) and second (T2) measurement in the CDH group were assessed by the Student's t-test for paired values. For each set of measurement (T1 and T2) the values were compared with HI by Student's t-test. RESULTS: Mean age at test was 7.5 +/- 5.2 months for HI, 4.5 +/- 2.5 at T1 and 11.9 +/- 4.5 months at T2 for CDH infants. At T1 there were no significant differences between CDH infants and HI in Vt, Crs, and FRC, while tPTEF/te ratio was lower and RR, Rrs, and LCI were higher in CDH patients than in HI. At T2 Vt, Crs, and FRC remained normal in CDH patients as well as RR that, at this time was not different between CDH and healthy infants; tPTEF/te remained below and Rrs and LCI remained above normal ranges, indicating a persistent impairment in lower airways patency. CONCLUSIONS: Lung function in infants with severe CDH is characterized by a persistent impairment in airways patency and significant inhomogeneity of ventilation, suggesting a peripheral bronchial obstruction even if the other lung function tests are within normal ranges.     

Effects of maternal retinoic acid administration in a congenital diaphragmatic hernia rabbit model

Maternal retinoid administration has beneficial effects on lung development in the nitrofen rodent toxic model of congenital diaphragmatic hernia (DH). We wanted to investigate the effects in a surgical model, where the retinoid signaling pathway is not primarily disrupted by the toxic agent. We created DH in fetal rabbits at day 23 of gestation, administrated to the does all trans-retinoic acid (ATRA) or vehicle (VHC) intramuscularly for 8 consecutive days and harvested normal and operated (DH) fetuses at 31 d (n = 7 in each group). Normal lungs exposed to ATRA had increased surfactant protein mRNA levels without change in type II pneumocyte density. There was no measurable effect on lung-to-body weight ratio and airway morphometry by ATRA. In DH lungs (DH/VHC) surfactant protein mRNA levels were increased, as well as the density of type II pneumocytes. When supplemented with ATRA (DH/ATRA) these parameters returned to normal (VHC). Cell proliferation or apoptosis were not influenced by ATRA supplementation. In conclusion, maternal ATRA supplementation does not affect gross anatomic, morphologic or proliferation indices in hypoplastic lungs related to surgically induced DH in rabbit. However, ATRA lowers surfactant protein expression and normalizes type I/II pneumocyte ratio to what is observed in normal lungs.     

Long-term pulmonary morbidity in survivors of congenital diaphragmatic hernia

Our objective was to study long-term respiratory outcomes of congenital diaphragmatic hernia (CDH) treated in the perinatal period. This was a cohort study with 26 adolescent survivors and age- and gender-matched controls. Medical histories were retrieved from hospital charts and questionnaires. Pulmonary function testing included measurement of maximum inspiratory and expiratory pressures (MIPS and MEPS) and maximum voluntary ventilation (MVV). Unpaired two-tailed t-test and nonlinear regression were used for statistical analysis. Significant differences were found in forced expiratory volume in one second (FEV(1)) (79% +/- 16% vs. 94% +/- 10%, P < 0.001), FEF(25-75) (62% +/- 24% vs. 84% +/- 15%, P < 0.001), FRC (114% +/- 20% vs. 95% +/- 13%, P < 0.001), RV/TLC (31% +/- 10% vs. 22% +/- 6%, P < 0.001), MVV (74% +/- 16% vs. 90% +/- 13%, P < 0.001), and MIPS (69% +/- 19% vs. 84% +/- 16%, P < 0.01), with numbers indicating percent predicted of reference values +/- SD. Reduction of MVV was not independent from FEV1 (r = 0.83). Forty-eight percent of patients vs. 4% of controls showed significant improvement of FEV1 after bronchodilators (86% +/- 15 vs. 98% +/- 10, P < 0.01). Forty-six percent of patients had abnormalities of the chest wall or spinal column such as pectus excavatum, pectus carinatum, and scoliosis, mostly mild or moderate. In conclusion, long-term respiratory outcome in adolescent CDH is associated with mild to moderate airway obstruction, a high prevalence of response to bronchodilators, and decreased inspiratory muscle strength. This should guide follow-up scheduling and should be taken into account for perioperative and critical care management.     

Physical activity, fitness, and dyspnea perception in children with congenital diaphragmatic hernia

We assessed whether physical activity could influence the performance and perception of dyspnea in children who were operated on for high risk congenital diaphragmatic hernia (CDH). We hypothesized that CDH children with normal activity would have better lung function and exercise performance level when compared to sedentary CDH subjects. We studied 18 children (11 males and 7 females, mean age 6.6 ± 2.6 years) who were surgically corrected. All children underwent physical examination, ECG at rest, and a maximal exercise stress test on a treadmill to measure the duration of exercise, maximal heart rate and blood pressure, maximal oxygen uptake (VO₂ max and VO₂ ml/kg/min). Lung function testing to measure forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV₁), and peak expiratory flow (PEF) was also performed. Following the stress test, the Dalhousie dyspnea and effort scale was shown to children as a pictorial panel with three groups of increasing (from 1 to 7) levels of effort perception, throat discomfort, and chest dyspnea. Children were divided into group A (sedentary) and group B (regular physical participation). There was no difference in CDH severity between the two groups. Group A had a statistically significant lower duration of exercise (P < 0.01), maximal oxygen consumption (VO₂ max P < 0.0001), VO₂ ml/kg/min (P < 0.001), higher throat closing feeling (P < 0.004), chest dyspnea (P < 0.001), and effort perception (P < 0.04) compared to group B. No differences were found in lung function tests. In conclusion, our data may suggest that children with a history of CDH who are active maintain a higher level of performance with less perception of dyspnea and effort. Pediatr. Pulmonol. 2011; 46:1000–1006. © 2011 Wiley‐Liss, Inc.     

Pulmonary function and exercise testing in adult survivors of congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is accompanied by pulmonary hypoplasia and structural abnormalities of the pulmonary vascular bed. It is unknown whether pulmonary function, exercise capacity, and gas exchange during exercise are impaired in adult CDH survivors. The objective of this study was to assess the long-term pulmonary function, exercise capacity, and gas exchange during exercise and relate these findings with quality of life. Of the 23 patients eligible for this study, 12 adult CDH survivors (mean age, 24.3 +/- 4.1 years) with high-risk CDH agreed to participate. Pulmonary function tests, diffusion capacity, and a cardiopulmonary exercise test (CPET) were performed. The FEV1 (mean z-score +/- SD; -1.30 +/- 1.37), FEF25-75% (-1.49 +/- 1.14), and the KCO (-1.03 +/- 1.24) were found to be lower in CDH survivors. The RV/TLC ratio (28.2% +/- 5.0%) was found to be higher. Despite these abnormalities, percent predicted work load (102% +/- 17.2%) and percent predicted maximal oxygen uptake (90.8% +/- 18.9%) were normal in most of the patients. The quality of life of CDH survivors, assessed with the SF-36 questionnaire, is comparable to the general population. Comparison of participants to non-participants did not reveal significant differences in clinical characteristics. In this first study assessing pulmonary function in adult survivors of CDH, mild airway obstruction was observed in most of the patients together with a slightly reduced diffusion capacity for CO. Exercise capacity and gas exchange parameters were normal in this group, indicating that patients do not have a physical impairment, as reflected by a normal quality of life of CDH patients.     

Correlation between lung scintigraphy and long-term outcome in survivors of congenital diaphragmatic hernia

Lung scintigraphy has been used to evaluate the degree of pulmonary hypoplasia in infants with congenital diaphragmatic hernia (CDH). However, the relationship between lung scintigraphy and long-term outcome of CDH remains unclear. The aim of this study is to determine whether lung scintigraphy correlates with long-term pulmonary morbidity and nutritional status in survivors of CDH. Consecutive 31 survivors of CDH were enrolled in this study. The initial scan was performed at 1-2 months when the patients were ready for discharge and the follow-up scan was performed following an approximately 1-year interval. The regional ventilation and perfusion were evaluated using (133)Xe-inhalation and intravenous (99m)Tc-MAA injection, respectively. The ventilation and perfusion of the ipsilateral lung was expressed as a percentage of that of the contralateral lung. Physical growth at 1 and 2 years, and pulmonary morbidity were reviewed from medical records. The ventilation and perfusion of the ipsilateral lung at the follow-up scan increased significantly from those at the initial scan. Ten patients had pulmonary morbidity. The ventilation and perfusion of the ipsilateral lung was significantly lower in the patients with pulmonary morbidity compared to the patients without pulmonary morbidity. The initial ventilation and perfusion of the ipsilateral lung were strongly correlated with body weight at 1 and 2 years (ventilation: R = 0.503, P < 0.01; perfusion: R = 0.760, P < 0.0001). These results suggest that lung scintigraphy is useful to predict long-term pulmonary morbidity and poor nutritional status in survivors of CDH.