An investigation on clinical differences between congenital pulmonary airway malformation and bronchial atresia.

BACKGROUND/PURPOSE: Differences in clinical features between congenital pulmonary airway malformation (CPAM) and bronchial atresia (BA) have not yet been clearly described. METHODS: We retrospectively reviewed 112 patients with a pathological diagnosis of CPAM or BA. The clinical parameters were statistically analyzed between these diseases. RESULTS: Seventy-one patients received prenatal diagnosis and 41 received postnatal diagnosis. The percentage of prenatal diagnosis was significantly higher in CPAM patients (84% vs 50%, p < 0.001). Among patients with prenatal diagnosis, the backgrounds were not different between the two diseases except for the number of Caesarean sections (81% vs 9%, p < 0.0001). The numbers of patients that underwent fetal interventions and emergent neonatal surgery were higher in CPAM (51% vs 15%, p < 0.01 and 76% vs 12%, p < 0.0001), although there was no statistical difference in survival rate (86% vs 97%, p = 0.2). In patients receiving postnatal diagnosis, pneumonia was the primary symptom in most BA patients, whereas respiratory distress was the major symptom in patients with CPAM. Age at presentation of the primary symptom was significantly older in BA patients (4.2 years vs 1.2 years, p < 0.005). CONCLUSION: CPAM and BA have distinct clinical features in terms of therapeutic and natural history. Careful imaging evaluation and pathological analysis can lead to an accurate diagnosis of BA. TYPE OF STUDY: Prognostic study. LEVEL OF EVIDENCE: Level II. This study is categorized as a "Prognostic Study" with LEVEL III of Evidence.

Risk of respiratory syncytial virus infection in infants with congenital cystic lung disease.

BACKGROUND: Congenital cystic lung disease (CCLD), which includes congenital cystic adenomatoid malformation, bronchopulmonary sequestration, and congenital lobar emphysema, has been reported to increase the risk of recurrent respiratory infection. In particular, respiratory syncytial virus (RSV) causes severe lower respiratory tract disease in high-risk infants. The objective of this study was to investigate the risk of severe RSV infection in infants with CCLD. METHODS: Infants antenatally diagnosed as having CCLD and admitted to a neonatal intensive care unit at the National Center for Child Health and Development in Tokyo between September 2002 and October 2011 were included in this study. We investigated retrospectively whether the infants were hospitalized with RSV infection by 24 months of age using their medical records. RESULTS: Forty-eight infants were antenatally diagnosed as having CCLD. Of the 48 infants, four (8.3%) were hospitalized with RSV infection by 24 months of age. CONCLUSIONS: Infants with CCLD have increased risk of severe RSV infection.

Mothers' knowledge about foreign body aspiration in young children.

OBJECTIVE: To evaluate parents' knowledge regarding foreign body aspiration (FBA) and determine the factors that are associated with lack of knowledge. METHODS: An 8-item questionnaire regarding knowledge of FBA was developed and distributed at regular check-ups for children younger than 24 months old. RESULTS: Out of the 1766 questionnaires distributed, 1603 were recovered and most of them (1539) were answered by mothers. After omitting 49 questionnaires with incomplete data, 1490 questionnaires answered by mothers were analyzed. Only 4.3% [95% CI 3.3-5.3] of mothers did not recognize a small toy as a cause of FBA, while 20.2% [95% CI 18.2-22.2] did not know that peanuts and other nuts can be causes of FBA, and 48.1% [95% CI 45.5-50.6] did not know that they should not give peanuts to a child younger than 3 years old. Regarding clinical signs, 27.7% [95% CI 25.4-30.0] and 41.8% [95% CI 39.3-44.3] of mothers did not know that sudden choking and sudden coughing were symptoms suggesting FBA, respectively. Being a mother with a child younger than 12 months old and being a mother with a first child were independent risk factors for lack of knowledge about FBA, regardless of the age of the mother. CONCLUSIONS: A substantial number of mothers lack knowledge regarding FBA. To prevent FBA and to make timely diagnoses, parents, especially mothers with children younger than 12 months old and mothers with a first child should be given adequate information.

Epidemiologic survey of patients with congenital central hypoventilation syndrome in Japan.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by hypoventilation during sleep. This study discusses the first epidemiologic survey of patients with CCHS in Japan. METHODS: The first survey was conducted between September and December 2006 and involved 507 registered institutes for pediatric training in Japan. The second survey was conducted between January and April 2007 and involved only those institutes that confirmed diagnosis of CCHS in the first survey or reported on CCHS at a conference during the preceding decade. RESULTS: Thirty-seven patients with CCHS were reported from 23 hospitals. Patient characteristics were as follows: 18 were male, 19 were female; and age range 4 months to 34 years. Diagnosis was based on clinical symptoms in 37/37 patients; blood gas analysis in 25/37; ventilatory response to inhaled CO(2) in 14/37; and genetic analysis (paired-like homeobox gene 2B) in 11/37. Complications included Hirschsprung's disease in 13/37 and central nervous system disorders in 15/37. Prognoses were as follows: 3/37 died in hospital, 1/37 remained in hospital, 33/37 were on home mechanical ventilation (died 4/33, survived 29/33), and 0/37 were cured. Ventilation methods included tracheostomy (21/37), use of a nasal mask (9/37), use of a facemask (5/37), and diaphragmatic pacing (1/37). CONCLUSIONS: There is currently no consensus on the most appropriate methods for diagnosing and treating patients with CCHS in Japan. More CCHS-related data need to be collected in the near future in order to enable appropriate diagnosis and management of patients with CCHS.

[A case of disseminated BCG infection found during treatment of an infant with Crohn's disease].

Bloody stools, diarrhea and perianal abscesses were observed from the age of two months infant. The boy received a BCG vaccination at the age of four months. The patient was diagnosed as having Crohn's disease at the age of six months by intestinal endoscopy. Based on the diagnosis, he was treated with nutrition therapy, salazosulfapyridine, and prednisolone. Fever of unknown origin occurred two months after he had taken azathioprine at the age of two years and two months. Mycobacterium tuberculosis was detected from a gastric aspirate, and he was diagnosed as having disseminated BCG infection by means of the multiplex PCR method. Chest CT showed miliary pulmonary nodules in both lungs on admission. Physical examination revealed enlarged lymphnodes, which were palpable around the neck and groin, and hepatomegaly. Laboratory data were within normal ranges except a slightly increased peripheral white blood cell and serum CRP level. He was treated with rifampicin (15 mg/kg/day), isoniazid (15 mg/kg/day) for 12 months, and streptomycin (25 mg/kg/day) for two months. He became afebrile a week after starting the treatment, and the miliary pulmonary nodules in both lungs had disappeared by 5 months after starting the treatment. An abnormality of the NEMO gene, which is the gene responsible for ectodermal dysplasia and immunodeficiency, was identified at the age of three years. It is assumed that an abnormality of the NEMO gene caused a latent BCG infection over a period of one year and ten months, and immunosuppressive medicine (azathioprine) induced a disseminated BCG infection. This case report supports that anti-tuberculosis medicine should be given to prevent disseminated BCG infection if an infant who receive immunosuppressive therapy is found to have an immune deficiency characterized by a mycobacterium infection after BCG vaccination.

Foreign body aspiration in children: a nationwide survey in Japan.

BACKGROUND: Foreign body aspiration (FBA) is a common cause for a respiratory emergency in young children and can be a life-threatening event. We, therefore, conducted the first nationwide survey in Japan. METHODS: We asked doctors of 261 tertiary hospitals across the nation to fill out a case card of FBA-diagnosed cases they had experienced for the past 2 years. In the case card, age and gender of the patients, elapsed time until being referred to the hospital, presenting symptoms, previous diagnosis, suspected aspiration episode, type and location of aspirated foreign body, and consequences were inquired. This retrospective survey was carried out during 21 months, since January 2005 through September 2006. RESULTS: Replies from 169 hospitals (64.8%) revealed that 163 cases of FBA had been treated in 114 hospitals during the past 2 years. Median age of cases was 1 year (2 months to 15 years), and 66.5% were male. Only 50.9% of the cases were referred to hospitals within 24h. Comparing these early-diagnosed cases, children with delayed diagnosis had similar age and sex distribution. In respect of presenting symptoms, characteristic ones such as choking or dyspnea were observed significantly more often in the early-diagnosed cases, whereas significantly predominant symptoms in children with delayed diagnosis were non-specific ones like coughing and wheezing (both, p<0.05). Although significantly more cases with early diagnosis reported suspected aspiration episodes (p<0.05), even in the delayed diagnosis group more than half cases (65%) had suspected episodes as well. Severe consequences occurred in seven cases (4.3%): four cases of irreversible hypoxic brain damage and one death due to multiorgan failure in the early diagnosis group; one bronchiectasis and one recurrent pneumonia in the delayed diagnosis group. CONCLUSIONS: Characteristics of FBA among children in Japan were not substantially different from the reports from other countries. Suspected episodes were important, and there were some differences in presenting symptoms between early and delayed diagnosis cases. However, there are still no key sings to make a prompt diagnosis. In order to prevent FBA and make a timely diagnosis, continuous and extensive educational programs should be provided.

Hyperventilation and finger exercise increase venous-arterial Pco2 and pH differences.

INTRODUCTION: Since the invention of the pulse oximeter, physicians often or even routinely perform venous blood gas analysis (VBGA). However, it has not been generally agreed that the application of VBGA is practically meaningful in routine clinical situations such as in an ED. METHODS: We measured venous-arterial Pco(2) difference ((v-a)Pco(2)) and arterial-venous pH difference ((a-v)pH), and analyzed the physiological factors that affect these differences in healthy volunteers and hyperventilation patients. RESULTS: In healthy volunteers, both (v-a)Pco(2) and (a-v)pH increased during finger exercise or hyperventilation in an intensity-dependent manner. Doppler echography indicated that increases in (v-a)Pco(2) and (a-v)pH during hyperventilation are induced by reduction of peripheral blood flow. Approximately 40% of patients with untreated respiratory alkalosis were found to be incorrectly diagnosed if based only on VBGA. CONCLUSIONS: It must be noted that VBGA may lead to overestimation of acidosis and to underestimation of respiratory alkalosis when extremities muscles are active or patients are hyperventilating. Physicians should keep these limitations in mind when conducting VBGA.

Resolution of hepatopulmonary syndrome after ligation of a portosystemic shunt in a pediatric patient with an Abernethy malformation.

This report describes a case of Abernethy malformation associated with hepatopulmonary syndrome, which was resolved after shunt ligation. The clinical course indicated that hepatopulmonary syndrome can develop in Abernethy malformation in which liver function and portal pressure is normal, and liver transplantation is not the exclusive therapy for hepatopulmonary syndrome. The levels of endotoxin and endothelin 1 in the shunt blood were high, whereas those of tumor necrosis factor alpha and interleukin-1beta were within reference range. Although pathogenesis of hepatopulmonary syndrome remains unknown, the findings in this case suggest that bacterial translocation as well as elevated endothelin 1 may play a causal role in development of hepatopulmonary syndrome.

X-linked severe combined immunodeficiency (X-SCID) with high blood levels of immunoglobulins and Aspergillus pneumonia successfully treated with micafangin followed by unrelated cord blood stem cell transplantation.

In this report, we describe a patient with X-linked severe combined immunodeficiency (X-SCID) who had high serum IgG, IgA, and IgM levels. The boy did well until 6 months of age, when he developed interstitial pneumonia caused by Aspergillus species, with a white cell count of 12,840/microL and only 10% lymphocytes; IgG, 991 mg/dL; IgA, 65 mg/dL; IgM, 472 mg/dL. Cell markers showed only 6.3% CD3, 2.1% CD4, 0.7% CD8, but 92% CD19 and 0.1% CD16+CD56+ (NK cells). A mutation was detected within exon 2 (C196 A-->C), leading to the substitution of proline for glutamine, which has not been reported previously. The boy was successfully treated with the new antifungal drug, micafangin (MCFG), at 5 mg/kg/day for 89 days. After resolution of the pneumonia, the patient underwent successful hematopoietic stem cell transplantation with completely matched unrelated female cord blood. The CD34 stem cell dose was 3.4 x 10(4) cells/kg. In conclusion, MCFG can be a first line agent for Aspergillus pneumonia in immunocompromised hosts.

Hepatopulmonary syndrome can show spontaneous resolution: possible mechanism of portopulmonary hypertension overlap?

Hepatopulmonary syndrome (HPS) (hypoxaemia due to intrapulmonary vasodilation and a right-to-left shunt associated with liver disease) resolves after liver transplantation. The authors describe a case of spontaneous resolution of HPS prior to liver transplantation. This patient was diagnosed with HPS associated with extra-hepatic biliary atresia when she was 10 years old. She exhibited digital clubbing, facial vascular dilation, cyanosis, and suffered from dyspnoea during exercise. The patient's PaO(2) at rest was 53.8 mm Hg in room air and a Technetium-99m macro-aggregated albumin lung perfusion scan demonstrated a right-to-left shunt. Although her symptoms and laboratory data supported a diagnosis of HPS, she nevertheless showed spontaneous resolution within 2 years. When she was 14 years old, pulmonary hypertension was evident upon examination of her echocardiogram. HPS may be improved or masked by an accidental overlap with pulmonary hypertension in the terminal stage of liver disease.

Congenital bronchial atresia in infants and children.

BACKGROUND/PURPOSE: Congenital bronchial atresia (CBA) usually presents incidentally in asymptomatic young male adults but is rarely diagnosed in children. The aim of this study was to clarify the clinical characteristics of CBA in childhood and to describe the spectrum of this condition. METHODS: The clinical features in 29 patients with CBA, aged from 1 day to 13 years (median, 4 years), were reviewed retrospectively. Diagnosis was confirmed by pathological findings of a blind-ending bronchus associated with distal mucous-filled bronchocele surrounded by hyperinflated lung parenchyma. RESULTS: All but 1 patient were symptomatic. The most frequent symptom was productive cough and fever owing to recurrent pneumonia found in 26 children. Two infants suffered from respiratory distress. Chest x-ray showed various findings of infiltrative pneumonia, emphysema, and a large cyst. Computed tomography, bronchography, and bronchoscopy were useful modalities for demonstrating bronchocele associated with hyperinflated lung or proximal blind-ending bronchus even in infected cases. The right lower lobe was predominantly affected in 12 cases, followed by left or right upper lobe in 7 cases. Lobectomy or segmentectomy resulted in remarkable clinical improvement. CONCLUSIONS: Congenital bronchial atresia presents differently in children than in young adults. Modern imaging techniques and careful pathological analyses lead to an accurate diagnosis of bronchial atresia, which may be misdiagnosed as intralobar sequestration or pulmonary bronchial cysts. Bronchial atresia is a distinct pathological entity that accounts for recurrent pneumonia or respiratory distress in childhood, requiring surgical treatment.

Hepatocyte growth factor protects small airway epithelial cells from apoptosis induced by tumor necrosis factor-alpha or oxidative stress.

Involvement of hepatocyte growth factor (HGF) in lung morphogenesis and regeneration has been established by in vitro and in vivo experiments in animals. In the present study, the protective activity of HGF against tumor necrosis factor (TNF)-alpha or hydrogen peroxide (H2O2)-induced damage of pulmonary epithelial cells was examined using the human small airway epithelial cell line (SAEC). Western blot analysis revealed that the receptor for HGF (c-Met) was highly expressed on the surface of SAEC and its downstream signal transduction pathway was functional. The SAEC was induced into apoptosis by the treatment with TNF-alpha or H2O2 in a dose-dependant manner, but was significantly rescued from apoptosis in the presence of HGF. The HGF effect was evident when added not only at the same time but also within several hours after treatment. This protective activity of HGF against the TNF-alpha- or H2O2-induced apoptosis was mediated, at least in part, by up-regulating the nuclear factor kappaB activity and an increase in the ratio of apoptosis-suppressing to apoptosis-inducing proteins. These results suggest that administration of HGF might exhibit a potent function in vivo for protection and improvement of acute and chronic lung injuries induced by inflammation and/or oxidative stress.