Interstitial Lung Disease In Children Research Articles

(1360) - Paediatric Lung Transplantation for Childhood Interstitial Lung Disease Shows Favorable Outcome Compared with LuTx for Cystic Fibrosis or Pulmonary Hypertension

(1360) - Paediatric Lung Transplantation for Childhood Interstitial Lung Disease Shows Favorable Outcome Compared with LuTx for Cystic Fibrosis or Pulmonary Hypertension

Introduction of European diagnostic workup of childhood interstitial lung disease

Introduction of European diagnostic workup of childhood interstitial lung disease

Estimating the effect of nintedanib on forced vital capacity in children and adolescents with fibrosing interstitial lung disease using a Bayesian dynamic borrowing approach.

The rarity of childhood interstitial lung disease (chILD) makes it challenging to conduct powered trials. In the InPedILD trial, among 39 children and adolescents with fibrosing ILD, there was a numerical benefit of nintedanib versus placebo on change in forced vital capacity (FVC) over 24 weeks (difference in mean change in FVC % predicted of 1.21 [95% confidence interval: -3.40, 5.81]). Nintedanib has shown a consistent effect on FVC across populations of adults with different diagnoses of fibrosing ILD. In a Bayesian dynamic borrowing analysis, prespecified before data unblinding, we incorporated data on the effect of nintedanib in adults and the data from the InPedILD trial to estimate the effect of nintedanib on FVC in children and adolescents with fibrosing ILD. The data from adults were represented as a meta-analytic predictive (MAP) prior distribution with mean 1.69 (95% credible interval: 0.49, 3.08). The adult data were weighted according to expert judgment on their relevance to the efficacy of nintedanib in chILD, obtained in a formal elicitation exercise. Combined data from the MAP prior and InPedILD trial analyzed within the Bayesian framework resulted in a median difference between nintedanib and placebo in change in FVC % predicted at Week 24 of 1.63 (95% credible interval: -0.69, 3.40). The posterior probability for superiority of nintedanib versus placebo was 95.5%, reaching the predefined success criterion of at least 90%. These findings, together with the safety data from the InPedILD trial, support the use of nintedanib in children and adolescents with fibrosing ILDs.

Long-term effects of high-dose systemic corticosteroids on growth and bone mineral density in patients treated for childhood interstitial lung disease (chILD).

Children's interstitial lung disease (chILD) is a rare and potentially life-threatening condition. For many chILD conditions, systemic corticosteroids (sCCS) are considered the primary treatment despite a broad spectrum of potential side effects. We aimed to determine the long-term effects of sCCS treatment on growth, bone mineral density (BMD), and body composition after chILD. This descriptive cross-sectional single-center study included patients diagnosed with chILD before the age of 18 years treated with sCCS in the period 1998-2020. Dual-energy X-ray absorptiometry, anthropometric measurements, bone age determination, and blood tests were performed in 53 (55% males) of 89 eligible patients. Median (range) age was 19.3 (6.4;30.7 years). Participants received a median (range) cumulative sCCS dose of 1144 (135; 6178) mg over a 2.0 (0.1; 13.8) years period and latest dose was administered 11.7 (1.2; 19.6) years before follow-up. Mean delta height (height standard deviation scores[SDS] - target height SDS) was reduced at sCCS treatment initiation (mean: -0.55, 95% confidence interval [CI]: -0.91; -0.20, p < .005) and at sCCS treatment cessation (mean: -0.86, 95%CI:-1.22; -0.51, p < .001), but normalized in the majority at follow-up (mean: -0.29, 95%CI:-0.61; 0.03, p = .07). Mean (SD) BMD z-score for the spine and whole body was -0.34 (1.06) and 0.52 (1.13), with no significant correlation to sCCS dose. Excess body fat (>30% in females, >25% in males) was found in 58% of patients. Long-term treatment with sCCS did not cause significant long-term reduction of height but showed subtle effects on fat mass percentage and BMD. Given the severity of chILD, the observed long-term effects of sCCS on growth and BMD appear acceptable.

Human pluripotent stem cell modeling of alveolar type 2 cell dysfunction caused by ABCA3 mutations.

Mutations in ATP-binding cassette A3 (ABCA3), a phospholipid transporter critical for surfactant homeostasis in pulmonary alveolar type II epithelial cells (AEC2s), are the most common genetic causes of childhood interstitial lung disease (chILD). Treatments for patients with pathological variants of ABCA3 mutations are limited, in part due to a lack of understanding of disease pathogenesis resulting from an inability to access primary AEC2s from affected children. Here, we report the generation of AEC2s from affected patient induced pluripotent stem cells (iPSCs) carrying homozygous versions of multiple ABCA3 mutations. We generated syngeneic CRISPR/Cas9 gene-corrected and uncorrected iPSCs and ABCA3-mutant knockin ABCA3:GFP fusion reporter lines for in vitro disease modeling. We observed an expected decreased capacity for surfactant secretion in ABCA3-mutant iPSC-derived AEC2s (iAEC2s), but we also found an unexpected epithelial-intrinsic aberrant phenotype in mutant iAEC2s, presenting as diminished progenitor potential, increased NFκB signaling, and the production of pro-inflammatory cytokines. The ABCA3:GFP fusion reporter permitted mutant-specific, quantifiable characterization of lamellar body size and ABCA3 protein trafficking, functional features that are perturbed depending on ABCA3 mutation type. Our disease model provides a platform for understanding ABCA3 mutation-mediated mechanisms of alveolar epithelial cell dysfunction that may trigger chILD pathogenesis.

Childhood interstitial lung disease: When to suspect and what to do

Childhood Interstitial lung Disease (chILD) is a heterogeneous group of more than 200 respiratory disorders characterized by the impairement of alveolar-capillary gas exchange and lung function. These disorders usually have a chronic course. Morbidity and mortality greatly vary depending on the disorder considered. Interstitial lung disease are associated with respiratory distress. During infancy the most common symptom to pay attention to is tachypnea, whilst in older children clinical presentation may be more insidious. When chILD is suspected, it is advisable to send the patient to a pediatric pulmonology center in order to set up a diagnostic work-up and an adequate treatment. A European protocol called the “Delphi method” has been standardizing empirical treatment since 2015.

The significance of multidisciplinary team meetings in diagnosing and managing childhood interstitial lung disease within the RespiRare network.

Childhood Interstitial Lung Disease (chILD) represents a rare and severe group of diseases for which the etiologic workup, classification, and management remain a challenge for most pediatric pulmonologists. In France in 2018, the RespiRare network established the first multidisciplinary team meetings (MDTm) dedicated to chILD. This study aims to investigate the impact of MDTm in chILD diagnosis and management as well as user satisfaction. The MDTm took place on a monthly basis through video conferences. The participants consisted of a quorum and included pediatric pulmonologists, radiologists, geneticists, and pulmonologists, with an average of 10.5 participants per meeting. Patients provided consent to participate in MDTm and for data collection. Data were retrospectively extracted from MDTm reports. To evaluate the usefulness of the MDTm and the satisfaction of the participants, a survey was sent by email at least 3 months after the MDTm to the participants. A total of 216 chILD cases were discussed during 56 MDTm sessions. The median age of onset was 0.5 years (interquartile range 0-7). The MDTm sessions resulted in the correction of chILD etiology in 25% of cases (neuroendocrine cell hyperplasia of infancy 17%, surfactant metabolism disorder 8%, pulmonary alveolar proteinosis 4%, hemosiderosis 3%, sarcoidosis 3%, and others 34%), and chILD was ruled out in 7% of cases. A change in therapy was proposed for 46% of cases. User satisfaction was significant, particularly regarding their confidence in managing these rare diseases. Dedicated MDTm sessions offer a unique opportunity to enhance chILD etiologic diagnosis and management, leading to increased physician knowledge and confidence in managing these patients.

Emerging Treatments for Childhood Interstitial Lung Disease.

Childhood interstitial lung disease (chILD) is a large and heterogeneous group of disorders characterized by diffuse lung parenchymal markings on chest imaging and clinical signs such as dyspnea and hypoxemia from functional impairment. While some children already present in the neonatal period with interstitial lung disease (ILD), others develop ILD during their childhood and adolescence. A timely and accurate diagnosis is essential to gauge treatment and improve prognosis. Supportive care can reduce symptoms and positively influence patients' quality of life; however, there is no cure for many of the chILDs. Current therapeutic options include anti-inflammatory or immunosuppressive drugs. Due to the rarity of the conditions and paucity of research in this field, most treatments are empirical and based on case series, and less than a handful of small, randomized trials have been conducted thus far. A trial on hydroxychloroquine yielded good safety but a much smaller effect size than anticipated. A trial in fibrotic disease with the multitargeted tyrosine kinase inhibitor nintedanib showed similar pharmacokinetics and safety as in adults. The unmet need for the treatment of chILDs remains high. This article summarizes current treatments and explores potential therapeutic options for patients suffering from chILD.

Hyperoxic ventilatory response in infants is related to nocturnal hypoxaemia

BackgroundThe carotid bodies primarily serve as oxaemia sensors that affect tidal breathing. Their function has not yet been studied in infants with nocturnal hypoxaemia. This cross-sectional study aimed to characterise the hyperoxic ventilatory response (HVR) in infants and its relationship to nocturnal hypoxaemia.MethodsThe HVR was analysed in term infants aged &lt;24 months with childhood interstitial lung disease (chILD), those with severe recurrent wheezing (wheeze), and nonrespiratory controls. The HVR timing was characterised using hyperoxia response time (HRT1), and HVR magnitude was characterised by the relative change in minute volume between normoxia and 30-s hyperoxia (VE_dH30). Time spent with an arterial haemoglobin oxygen saturation (SpO2) &lt;90% during overnight monitoring (t90) was estimated.ResultsHVR data were available for 23 infants with chILD, 24 wheeze and 14 control infants. A significant decrease in minute volume under 30 s of hyperoxia was observed in all patients. HRT1 was shorter in chILD (5.6±1.2 s) and wheeze (5.9±1.5 s) groups than in the controls (12.6±5.5 s) (ANOVA p&lt;0.001).VE_dH30 was increased in the chILD group (24.3±8.0%) compared with that in the controls (14.7±9.2%) (p=0.003).t90was abnormal in the wheeze (8.0±5.0%) and chILD (32.7±25.8%) groups and higher in the chILD group than in the controls (p&lt;0.001). HRT1 negatively correlated witht90in all groups.ConclusionSignificant differences in HVR timing and magnitude were noted in the chILD, wheeze and control groups. A relationship between nocturnal hypoxaemia and HRT1 was proposed. HVR characterisation may help identify patients with abnormal nocturnalSpO2.

Childhood interstitial lung disease in Turkey: first data from the national registry.

The childhood interstitial lung diseases (chILD) Turkey registry (chILD-TR) was established in November 2021 to increase awareness of disease, and in collaboration with the centers to improve the diagnostic and treatment standards. Here, the first results of the chILD registry system were presented.In this prospective cohort study, data were collected using a data-entry software system. The demographic characteristics, clinical, laboratory, radiologic findings, diagnoses, and treatment characteristics of the patients were evaluated. Clinical characteristics were compared between two main chILD groups ((A) diffuse parenchymal lung diseases (DPLD) disorders manifesting primarily in infancy [group1] and (B) DPLD disorders occurring at all ages [group 2]).There were 416 patients registered from 19 centers. Forty-six patients were excluded due to missing information. The median age of diagnosis of the patients was 6.05 (1.3-11.6) years. Across the study population (n = 370), 81 (21.8%) were in group 1, and 289 (78.1%) were in group 2. The median weight z-score was significantly lower in group 1 (- 2.0 [- 3.36 to - 0.81]) than in group 2 (- 0.80 [- 1.7 to 0.20]) (p < 0.001). When we compared the groups according to chest CT findings, ground-glass opacities were significantly more common in group 1, and nodular opacities, bronchiectasis, mosaic perfusion, and mediastinal lymphadenopathy were significantly more common in group 2. Out of the overall study population, 67.8% were undergoing some form of treatment. The use of oral steroids was significantly higher in group 2 than in group 1 (40.6% vs. 23.3%, respectively; p = 0.040). Conclusion: This study showed that national registry allowed to obtain information about the frequency, types, and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. What is Known: • Childhood interstitial lung diseases comprise many diverse entities which are challenging to diagnose and manage. What is New: • This study showed that national registry allowed to obtain information about the frequency, types and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. Also, our findings reveal that nutrition should be considered in all patients with chILD, especially in A-DPLD disorders manifesting primarily in infancy.

ИНТЕРСТИЦИАЛЬНЫЕ ЗАБОЛЕВАНИЯ ЛЕГКИХ У ДЕТЕЙ: СОВРЕМЕННАЯ КЛАССИФИКАЦИЯ, АЛГОРИТМ ДИАГНОСТИКИ, ОБЩИЕ ПОДХОДЫ К ТЕРАПИИ

Authors, based on bibliographical research and their own data, provide up-to-date information on interstitial lung diseases (ILD) in children. The classification of ILD in children that is used in the registry of pediatric patients with ILD in the European Union (2022) with a critical analysis is given, and the need for its practical use is substantiated. The algorithm for diagnosing childhood ILD is described in detail starting with the diagnostic criteria for childhood ILD syndrome and possible complications. The algorithm includes step-by-step, sequential steps to diagnose these rare diseases. Taking into account the latest advances in genetics and molecular biology, the main proteins and their encoding genes associated with ILD, types of inheritance and phenotypes are listed as well. Indications and findings during lung biopsy, general approaches to the treatment of ILD in children, including oxygen therapy, drug therapy and other therapy, taking into account the existing consensus of experts, are characterized.

A rare case of childhood interstitial lung disease attributed to desquamative interstitial pneumonia

Desquamative interstitial pneumonia (DIP) is a rare form of interstitial lung disease (ILD) in children that can be idiopathic but is usually associated with an inborn error of surfactant metabolism. We reported DIP in a 13-year-old girl who was referred to our outpatient clinic because of worsening dyspnea. High-resolution computed tomography showed ground-glass attenuation with honeycombing and intralobular, interstitial septal thickening, suggestive of an ILD. Transbronchial lung biopsy was performed, and histopathology findings were consistent with DIP. The patient was started on steroid therapy with oxygen support. Unfortunately, she died a month after being diagnosed due to disease progression.

Clinical features and outcomes of children’s interstitial lung disease accompanied with connective tissue disease: A prospective cohort study

BackgroundMedical complexity of childhood interstitial lung disease (chILD) with connective tissue disease (CTD) poses a considerable challenge to pediatricians. MethodsClinical characteristics, laboratory findings, pulmonary function tests (PFTs), treatments and outcomes obtained for patients with CTD-chILD were analyzed in a prospective study. ResultsPatients’ median age at diagnosis was 7 years old. About 29.4% (15/51) suffered rapidly progressive childhood ILD (RP-chILD) with a high mortality rate (33.3%, 5/15), and the incidence of RP-chILD in juvenile idiopathic inflammatory myopathies was as high as 41.6% and the mortality rate was 30% (3/10). More than 70% patients had decreased diffusion capacity. The mean interval from symptoms-onset to diagnosis was 11.3 months. Compared to chILD with known CTD, the chILD proceeded CTD had a longer diagnosis interval, higher mortality, hospital stays and costs (P < 0.05). Lung imaging (33.3%) and lung function (72.7%) were partially reversible. The average survival time was 68.6 months. Cox univariate analysis showed that HRCT score ≥3, experiencing RP-chILD, cyanosis, acute respiratory distress syndrome (ARDS) and CD4 T cell <200 were significant predictors of death for chILD, whereas Cox multivariate analysis showed that ARDS was significant predictor of death for CTD-chILD, while IVIG support combined with corticosteroids and immunosuppressants was a protective factor. ConclusionsCare providers should conduct an assessment for CTD in chILD as a longer interval between the diagnosis of chILD and the CTD is associated with increased mortality. Complications as ARDS predict poor outcome in CTD-chILD, while IVIG support combined with corticosteroids and immunosuppressants is a protective factor.

Variants in FGF10 cause early onset of severe childhood interstitial lung disease: A detailed description of four affected children.

Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well-established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the FGF10 gene are known causes of the lacrimo-auriculo-dento-digital (LADD) syndrome and aplasia of lacrimal and salivary glands.Previous studies indicate that pathogenic variants in FGF10 can cause childhood Interstitial Lung Disease (chILD) due to severe diffuse developmental disorders of the lung, but detailed reports on clinical presentation and follow-up of affected children are lacking. We describe four children with postnatal onset of chILD and heterozygous variants in FGF10, each detected by exome or whole genome sequencing. All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years due to right heart failure related to severe pulmonary hypertension (PH) and one patient is alive at age of 6years, but still symptomatic. Histopathological analysis of lung biopsies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia and interstitial fibrosis. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis. Our report extends the phenotype of FGF10-related disorders to early onset chILD with progressive interstitial lung fibrosis and PH. Therefore, FGF10-related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints and PH.

Modern concepts of clinical variants and features of hypersensitivity pneumonitis in children

Hypersensitivity pneumonitis (HP) (J67) is the most common interstitial lung disease in children and adolescents. The disease is immunologically determined, it can be a disease when exposed to various factors that cause harmful effects on the environment. The most significant are thermophilic actinomycetes, antigens of animal and fungal origin. Currently, cases of “two cases of infection” have been identified, when a genetic predisposition has been identified in case of detection of cases of antigen results in the implementation of diseases. Immunological studies in GP are mainly focused on identifying specific IgG to the “guilty” antigen. High-resolution computed tomography is the most sensitive method of visualizing the GP, pathological changes are detected in more than 90% of patients. According to the characteristics of the clinical course and duration of the disease, acute (lasting less than 6 months) and chronic (more than 6 months) variants of the disease are distinguished. The formation of fibrosis of the lung tissue up to the honeycomb lung is observed in approximately 18% of cases. There are variants of HP: with fibrous and non-fibrous (inflammatory) phenotype. The basis of drug therapy so far is systemic and inhaled glucocorticosteroids, the use of which is pathogenetically substantiated and clinically effective. The prospects for therapy are also associated with the use of antifibrotic drugs: pirfenidone and nintedanib, which slow down the decline in lung function and improve patient survival. At the same time, the exclusion of contact with a causally significant allergen plays a key role. Our own observations concern 280 children with GP aged 8 months to 16 years, including 70 patients in the first year of life. Most patients had a hereditary allergic burden (in 74%) and a causal factor was traced. The prognosis, with rare exceptions, was favorable. The main reasons for poor outcomes in GP are continued contact with a causally significant allergen, late diagnosis of the disease, and inadequate therapy.

Pediatric Pulmonology 2022 year in review: Rare and diffuse lung disease.

The field of rare and diffuse pediatric lung disease continues to evolve and expand rapidly as clinicians and researchers make advancements in the diagnosis and treatment of children's interstitial and diffuse lung disease, non-cystic fibrosis bronchiectasis, and primary ciliary dyskinesia. Papers published on these topics in Pediatric Pulmonology and other journals in 2022 describe newly recognized disorders, elucidate disease mechanisms and courses, explore potential biomarkers, and assess novel treatments. In this review, we will discuss these important advancements and place them in the context of existing literature.

Clinical scope and healthcare utilization in childhood interstitial lung disease at a tertiary center.

Childhood interstitial lung disease (chILD) is a heterogeneous group of diffuse lung diseases that can be challenging to diagnose. With relative rarity of individual entities, data are limited on disease prevalence, care patterns, and healthcare utilization. The objective of this study was to evaluate chILD prevalence and review diagnostic and clinical care patterns at our center. A single-center, retrospective cohort study was conducted of patients receiving care at the Children's Hospital of Philadelphia (CHOP) between 1 January 2019 and 31 December 2021. Through query of selected ICD-10 billing codes relevant for chILD and medical chart review, a total of 306 patients were identified receiving pulmonary care during this period. Respiratory symptom onset was documented to have developed before 2 years of age for 40% of cases. The most common diagnostic categories included those with oncologic disease (21.2%), bronchiolitis obliterans (10.1%), and connective tissue disease (9.5%). Genetic testing was performed in 49% of cases, while 36% underwent lung biopsy. Hospitalization at CHOP had occurred for 80.4% of patients, with 45.1% ever hospitalized in an intensive care unit. One-third of children had required chronic supplemental oxygen. Seven (2.3%) patients died during this 3-year period. Collectively, these data demonstrate the scope of chILD and extent of health care utilization at a large volume tertiary care center. This approach to cohort identification and EMR-driven data collection in chILD provides new opportunities for cohort analysis and will inform the feasibility of future studies.

An Update Review on Childhood Interstitial Lung Diseases (chILD)

In recent times, we have encountered several cases of Childhood Interstitial Lung Disease (chILD) in our clinical practice in Bangladesh. In developed world, there has been tremendous progress in the approach to chILD, with particular recognition that (chILD) in infants is often distinct from the forms that occur in older children and adults. Confirmation of diagnosis is challenging because of the rarity of Interstitial Lung Disease (ILD) and the fact that the presenting symptoms of ILD often overlap those of common respiratory disorders. There are few case reports and almost no study on chILD in Bangladesh from net search. A growing part of the etiologic spectrum of chILD is being attributed to molecular defects. The pathogenesis of the various chILD is complex and the diseases share common features of inflammatory and fibrotic changes of the lung parenchyma that impair gas exchanges. We are trying to diagnose chILD by excluding methods of suspected children in our aspects. However, in developed nations, clinical practice guidelines emphasize the role for high resolution computed tomography (HRCT) of chest, genetic testing, and lung biopsy in the diagnostic evaluation. Despite improvements in patient management, the therapeutic strategies are still relying mostly on corticosteroids although specific therapies are emerging. Larger longitudinal cohorts of patients are being gathered through on-going international collaborations to improve disease knowledge and targeted therapies. Thus, it is expected that children with ILD will be able to reach the adulthood transition in a better condition. The Journal of Ad-din Women's Medical College; Vol. 11 (2), July 2023; p 39-47

The USnational registry for childhood interstitial and diffuse lung disease: Report of study design and initial enrollment cohort.

Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children's Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders. This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.S. Clinical data are collected and managed using the Research Electronic Data Capture (REDCap) electronic data platform. We report the study design and selected elements of the initial Registry enrollment cohort, which includes 683 subjects with a broad range of chILD diagnoses. The most common diagnosis reported was neuroendocrine cell hyperplasia of infancy, with 155 (23%) subjects. Components of underlying disease biology were identified by enrolling sites, with cohorts of interstitial fibrosis, immune dysregulation, and airway disease being most commonly reported. Prominent morbidities affecting enrolled children included home supplemental oxygen use (63%) and failure to thrive (46%). This Registry is the largest longitudinal chILD cohort in the United States to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.

High NHLRC2 expression is associated with shortened survival in lung adenocarcinoma.

Certain variants of NHL repeat (named after NCL-1, HT2A and LIN-41)-containing protein 2 (NHLRC2) gene have been linked to severe fibrotic interstitial lung disease in children. The aim of the current study was to evaluate the expression of NHLRC2 in lung cell and tissue samples from patients with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The expression of NHLRC2 in lung tissue samples was studied by immunohistochemistry (102 ADC, 111 SCC), mRNA in situ hybridization (4 ADC, 3 SCC), and Western blot analysis (3 ADC, 2 SCC). The immunohistochemical NHLRC2 expression was measured by image analysis software and the percentage of NHLRC2-positive cancer cells was evaluated by semiquantitative analysis. The immunohistochemical results of NHLRC2 were compared with the clinical and histological characteristics of the patients. NHLRC2 protein levels in primary stromal and epithelial lung cancer cell lines were measured by Western blot analysis. NHLRC2 was mainly expressed in cancer cells and inflammatory cells within the tumor. The NHLRC2 expression evaluated by image analysis method was significantly higher in ADC compared with that in SCC (P<0.001). High NHLRC2 expression was associated with reduced disease specific survival (P=0.002), overall survival (P=0.001), and high mitotic activity (P=0.042) in ADC. Additionally, the proportion of NHLRC2-positive cancer cells analyzed by the semiquantitative method was significantly higher in ADC than in SCC (P<0.001). NHLRC2 expression was higher in lung ADC than in SCC and its expression was associated with poor survival in ADC patients. Further studies are required to clarify the pathogenetic role of NHLRC2 in lung cancer.