Large Airway Disease Research Articles

Neutrophilic inflammation in sputum or blood does not define a clinically distinct asthma phenotype in ATLANTIS

IntroductionNeutrophilic asthma has been suggested to be a clinically distinct phenotype characterized by more severe airflow obstruction and higher exacerbation risk. However, this has only been assessed in few and smaller studies, using different cut-offs to define neutrophilia, and with conflicting results.We used data from ATLANTIS, an observational longitudinal study including a large number of patients with asthma and healthy controls.AimTo examine if neutrophilic inflammation, either in sputum or blood, is more prevalent in asthma and whether it correlates with disease severity.MethodsATLANTIS included 773 asthma patients, with blood collected from 767 (99%) and sputum from 228 patients (30%). Data were available from 244 healthy controls, all providing blood and 126 (52%) providing sputum. Asthma patients were characterized including parameters of large and small airways disease at baseline and after 6- and 12-months follow-up. Sputum and blood neutrophilia were defined as values exceeding the upper quartile in asthma patients.ResultsThe prevalence of sputum neutrophilia did not differ between asthma patients and healthy controls. Asthma patients with sputum neutrophilia did not display more severe symptoms, large or small airways disease, or more frequent exacerbations. Blood neutrophilia was more common in asthma and associated with higher BMI, female sex, current smoking and systemic corticosteroid use. Patients with blood neutrophilia had a statistically significant, but small, increase in RV/TLC. Blood neutrophilia was not associated with large or small airways disease, or exacerbation risk.ConclusionSputum and blood neutrophilia do not define a distinct clinical phenotype in asthma.

Development and Disorders of the Airway in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD), a disorder characterized by arrested lung development, is a frequent cause of morbidity and mortality in premature infants. Parenchymal lung changes in BPD are relatively well-characterized and highly studied; however, there has been less emphasis placed on the role that airways disease plays in the pathophysiology of BPD. In preterm infants born between 22 and 32 weeks gestation, the conducting airways are fully formed but still immature and therefore susceptible to injury and further disruption of development. The arrest of maturation results in more compliant airways that are more susceptible to deformation and damage. Consequently, neonates with BPD are prone to developing airway pathology, particularly for patients who require intubation and positive-pressure ventilation. Airway pathology, which can be divided into large and small airways disease, results in increased respiratory morbidity in neonates with chronic lung disease of prematurity.

Occupational Lung Diseases: Spectrum of Common Imaging Manifestations.

Occupational lung diseases (OLD) are a group of preventable conditions caused by noxious inhalation exposure in the workplace. Workers in various industries are at a higher risk of developing OLD. Despite regulations contributing to a decreased incidence, OLD remain among the most frequently diagnosed work-related conditions, contributing to significant morbidity and mortality. A multidisciplinary discussion (MDD) is necessary for a timely diagnosis. Imaging, particularly computed tomography, plays a central role in diagnosing OLD and excluding other inhalational lung diseases. OLD can be broadly classified into fibrotic and non-fibrotic forms. Imaging reflects variable degrees of inflammation and fibrosis involving the airways, parenchyma, and pleura. Common manifestations include classical pneumoconioses, chronic granulomatous diseases (CGD), and small and large airway diseases. Imaging is influenced by the type of inciting exposure. The findings of airway disease may be subtle or solely uncovered upon expiration. High-resolution chest CT, including expiratory-phase imaging, should be performed in all patients with suspected OLD. Radiologists should familiarize themselves with these imaging features to improve diagnostic accuracy.

Small airway disease: A new “phenotype” of obstructive airway disease

Small airways are usually defined as noncartilaginous airways with an internal diameter <2 mm. Robust data are available regarding small airway involvement in various obstructive airway diseases such as bronchial asthma and chronic obstructive pulmonary disease (COPD). Small airway disease (SAD) can present as a starting point of emphysema, and in few cases, SAD can present with emphysema. Thus, SAD in COPD is a different phenotype along with emphysema and chronic bronchitis. Although bronchial asthma is a disease of large and medium size airways, small airway involvement has been documented in asthma in late stage. Involvement of small airways in asthma is a clinical clue toward the role of inhaled antimuscarinic therapy in this phenotype. Spirometry is a simple and cost-effective but less reliable test to diagnose SAD in comparison to impulse oscillometry. Inhalation therapy with small particle size aerosol long-acting beta-agonist plus inhaled corticosteroids is recommended for treatment of SAD. Targeting small airways in asthma and COPD with ultrafine particle-size inhaled medicines with antimuscarinic drugs will have a successful treatment outcome.

Anatomic study of the canine bronchial tree using silicone casts, radiography, and CT.

This prospective anatomic study examined the canine lower airway lumen morphology by visual inspection, radiography, and CT of silicone casts of two dogs. Study results showed the lobar, bronchopulmonary segmental, and pulmonary lobular organization of the lungs grossly reflected in the hierarchically clustered branching structure of the bronchial tree. Study results also provided a basis for differentiating bronchial and bronchiolar patterns. Whereas images of silicone-filled bronchial lumens produced large-diameter, branching, tapering bands that radiated from the lung hilus, the pattern was different for small airways. Images of silicone-filled bronchiole lumens produced small-diameter, branching, tapering, nonradiating lines that created a speckled pattern resembling micronodules and, unexpectedly during radiography, small-diameter rings with air-filled lumens attributed to positive and negative summation shadows. Consequently, imaging patterns in dogs might be affected by pulmonary lobular morphology and might differentiate large and small airway diseases.

Chronic obstructive pulmonary disease risk assessment tools: is one better than the others?

Purpose of reviewRisk assessment tools are essential in COPD care to help clinicians identify patients at higher risk of accelerated lung function decline, respiratory exacerbations, hospitalizations, and death.Recent findingsConventional methods of assessing risk have focused on spirometry, patient-reported symptoms, functional status, and a combination of these tools in composite indices. More recently, qualitatively and quantitatively assessed chest imaging findings, such as emphysema, large and small airways disease, and pulmonary vascular abnormalities have been associated with poor long-term outcomes in COPD patients. Although several blood and sputum biomarkers have been investigated for risk assessment in COPD, most still warrant further validation. Finally, novel remote digital monitoring technologies may be valuable to predict exacerbations but their large-scale performance, ease of implementation, and cost effectiveness remain to be determined.SummaryGiven the complex heterogeneity of COPD, any single metric is unlikely to fully capture the risk of poor long-term outcomes. Therefore, clinicians should review all available clinical data, including spirometry, symptom severity, functional status, chest imaging, and bloodwork, to guide personalized preventive care of COPD patients. The potential of machine learning tools and remote monitoring technologies to refine COPD risk assessment is promising but remains largely untapped pending further investigation.

CT Findings of Central Airway Lesions Causing Airway Stenosis-Visualization and Quantification: A Pictorial Essay.

The tracheobronchial tree is a system of airways that allows the passage of air to aerate the lungs and entire body. Several pathological conditions can affect this anatomical region. Multidetector CT (MDCT) helps identify and characterize various large airway diseases. Post-processing tools, such as virtual bronchoscopy and automatic lung analysis, can help enhance the performance of imaging studies. In this pictorial essay review, we provide imaging findings of various bronchial lesions manifested as wall thickening and endoluminal nodules on conventional MDCT and advanced image visualization and analysis.

Large airway diseases in pediatrics: a pictorial essay.

“Large airway diseases” is being used as an all-encompassing phrase to describe a broad spectrum of pathological entities, which involves the trachea, main, lobar, and segmental bronchi of up to 3 mm diameter. Imaging modalities such as radiography, computed tomography, and magnetic resonance imaging contribute to the identification and diagnosis of each entity. Knowledge of clinical information, normal cross-sectional anatomy, and imaging characteristics of large airway diseases is necessary for appropriate radiologic evaluation. This review provides information about congenital and acquired diseases of the large airways in the pediatric population.

Effect of small airways and viscoelasticity on lung mechanics from expiratory occlusion

Monitoring the decay rate of airflow in spirometry may be clinically useful. The decay rate is expected to represent a combination of lung elastance and airway resistance. However, the decay rate calculated using the single compartment lung model is not expected to account for slower lung mechanics, such as small airways resistance and tissue viscoelasticity. This study assesses whether the decay rate is affected by these lung mechanics. An exponentially decaying flow was created using a shutter to occlude airflow during passive expiration for 15 healthy subjects. To approximate small airways resistance and viscoelasticity, the gradient of pressure increase (relaxation gradient) during shutter closure was measured. The occlusion resistance, elastance, and decay rate were also calculated for these breaths. None of these mechanics were found to be correlated with the relaxation gradient. The relaxation gradient was also found to be independent of driving pressure. Conversely, the relaxation gradient was found to depend on lung volume. The results of this study suggest using lung mechanics and decay rate to monitor changes in lung condition over time may miss information about changes in the small airways and viscoelastic lung tissue. Thus, it is useful for monitoring large airways disease, but may be ineffective for small airways disease such as ARDS.

Progress in the imaging of COPD: quantitative and functional evaluation

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease, which has caused serious social and economic burden. The main characteristic of COPD is the heterogeneity of disease, manifesting as emphysema, functional small airways disease (fSAD) and large airway diseases. Imaging plays an important role in the evaluation of COPD. In this article, we summarized the recent advances in the imaging of COPD, especially in the quantitative and functional evaluations of the disease. Imaging provides the detailed anatomical, quantitative and function information, illustrates regional heterogeneity and spatial distribution, as well as provides microstructural assessment on the alveolar level. Especially, air trapping index (ATI), parametric response mapping (PRM), gas exchange and texture analysis facilitate the early diagnosis, phenotype classification, severity and therapeutic effect evaluation.

Pulmonary Complications of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease characterized by the production of pathogenic autoantibodies and immune complexes and is responsible for significant morbidity and mortality through a wide range of clinical manifestations which can affect almost any organ. Pulmonary involvement is prevalent and seen in 50 to 70% of SLE patients and may even be the presenting feature in 4 to 5% of patients. By 10 years postdiagnosis, 12% will have accumulated an element of permanent lung damage. Pulmonary complications are broad and include pleural disease, interstitial lung disease (ILD), vasculitis, pulmonary embolism, pulmonary hypertension, large airway disease, shrinking lung syndrome, and infection. Conditions can range mostly from asymptomatic, for example, in mild cases of pleural effusion or obstructive airway disease, to life-threatening disease, for example, in acute lupus pneumonitis or diffuse alveolar hemorrhage. ILD and pulmonary hypertension are both frequently seen in other autoimmune rheumatic diseases such as systemic sclerosis; however, in SLE, they tend to be milder and have a comparatively favorable prognosis. Although collectively pulmonary involvement in SLE is common, the heterogeneity of SLE and rareness of individual complications make clinical trials difficult and treatment is usually based on case series reports and anecdotal experience with various immunosuppressive agents. Some of these immunosuppressive agents such as azathioprine, methotrexate, and cyclophosphamide have also been linked with drug-induced lung injury.

A case report of primary anaplastic large cell lymphoma arising from the trachea

Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin’s lymphoma. Its presentation as an isolated primary lesion in the airway is extremely rare and not often considered in the differential diagnosis of airway lesions. Thus, it is important to be aware of its presenting manifestations, imaging features and treatment complications. Here, we report a case of pathologically confirmed tracheal-based ALCL. We especially focus on presenting the salient imaging features of this entity and the associated clinical and pathological findings of this rare large airway disease.

RECURRENT TRACHEOBRONCHIAL STENOSIS IN A PATIENT WITH LONG-STANDING INFLAMMATORY BOWEL DISEASE

SESSION TITLE: Pulmonary Manifestations of Systemic Diesase SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Respiratory tract involvement is not typically affiliated with Crohn's disease. Very few cases in literature have documented this association, and it is unknown if the respiratory symptoms correlate with GI symptomatology. It is thought that the large airway involvement is typically responsive to inhaled and systemic steroids. CASE PRESENTATION: 21 year old female with a history of Crohns disease diagnosed at the age of 11 presented with shortness of breath and hoarseness. She was found to have tracheal stenosis that over the course of the next several years was recurrent requiring repeated dilations and was also associated with bronchial stenosis bilaterally also requiring multiple dilation procedures. Biopsies showed acute inflammation with neutrophils, lymphoplasmacytic infiltrate, often with granulation tissue and occasional giant cells. Her respiratory involvement did not correlate with her GI symptoms and required multiple prolonged courses of oral steroids. Complicating the picture was a label of GPA due to sino-nasal disease but repeated ANCA levels were negative and rheumatology deemed her large airway disease to not be secondary to GPA. DISCUSSION: Large airway involvement in inflammatory bowel disease is rare and only a few cases have been reported in literature, the first in 1976. Typically the timeline and severity of airway involvement is independent of GI involvement from the disease. Important differentials to rule out are sarcoidosis, granulomatous polyangiitis, and tuberculosis. Noncaseating granulomas are rarely seen in biopsies which usually reveals neutrophilic, lymphoplasmacytic and macrophage infiltration. In more severe cases, tracheobronchial stenosis can occur although the large airway disease generally responds well to inhaled and systemic steroids. In our case the patient required multiple dilation procedures as well as prolonged steroids; at times in the intravenous form at high doses. CONCLUSIONS: Large airway involvement is a rare manifestation of Crohn's disease and doesn't necessarily respond to inhaled steroids and at times warrants long term high dose systemic steroid therapy as well as repeated tracheobronchial dilation procedures. Reference #1: Seunghyun Park, Jongha Park, Hyun-Kuk Kim et al. Tracheal Involvement in Crohn Disease: the First Case in Korea. Clin Endosc. 2016 Mar; 49(2): 202–206. Reference #2: Kuźniar T, Sleiman C, Brugière O, et al. Severe tracheobronchial stenosis in a patient with Crohn’s disease. Eur Respir J. 2000;15:209–212 Reference #3: Plataki M, Tzortzaki E, Lambiri I et al. Severe airway stenosis associated with Crohn’s disease: case report. BMC Pulm Med. 2006;6:7 DISCLOSURES: No relevant relationships by Hina Ahmed, source=Web Response

A Disintegrin and A Metalloproteinase-9 (ADAM9): A Novel Proteinase Culprit with Multifarious Contributions to COPD.

Proteinases with a disintegrin and a metalloproteinase domain (ADAMs) have not been well studied in COPD. We investigated whether ADAM9 is linked to COPD in humans and mice. ADAM9 blood and lung levels were measured in COPD patients versus controls, and air- versus cigarette smoke (CS)-exposed wild-type (WT) mice. WT and Adam9-/- mice were exposed to air or CS for 1-6 months, and COPD-like lung pathologies were measured. ADAM9 staining was increased in lung epithelial cells and macrophages in smokers and even more so in COPD patients and correlated directly with pack-year smoking history and inversely with airflow obstruction and/or FEV1 % predicted. Bronchial epithelial cell ADAM9 mRNA levels were higher in COPD patients than controls and correlated directly with pack-year smoking history. Plasma, BALF and sputum ADAM9 levels were similar in COPD patients and controls. CS exposure increased Adam9 levels in WT murine lungs. Adam9-/- mice were protected from emphysema development, small airway fibrosis, and airway mucus metaplasia. CS-exposed Adam9-/- mice had reduced lung macrophage counts, alveolar septal cell apoptosis, lung elastin degradation, and shedding of VEGFR2 and EGFR in BALF samples. Recombinant ADAM9 sheds EGF and VEGF receptors from epithelial cells to reduce activation of the Akt pro-survival pathway and increase cellular apoptosis. ADAM9 levels are increased in COPD lungs and linked to key clinical variables. Adam9 promotes emphysema development, and large and small airway disease in mice. Inhibition of ADAM9 could be a therapeutic approach for multiple COPD phenotypes.

COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series).

Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction/injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested on cell culture systems, animal models of COPD, and/or smokers and COPD patients.

Large and Small Airway Disease Related to Inflammatory Bowel Disease.

Although airway disease associated with inflammatory bowel disease is uncommon, its involvement may have severe clinical consequences. This article reviews the breadth of pathologic processes that can be expected in the various sizes of airways, and provides a differential diagnosis from other airway diseases that can be found in association with inflammatory bowel disease. It also makes suggestions as to how airway disease can be best differentiated by using appropriate special stains.

Updates on MRI Evaluation of Pediatric Large Airways.

The purposes of this article are to present a practical approach to imaging of common congenital and acquired diseases of the pediatric large airways with MRI and to describe the imaging findings. High-quality MRI of the airways is an increasingly feasible alternative to conventional radiography, fluoroscopy, and CT in the evaluation of many diseases of the pediatric large airways.

Precision medicine in COPD: Are we making it too difficult?

See article, page 322

Tracheopathia and tracheobronchopathia osteochondroplastica: Computed tomographic findings of an uncommon entity – a series of two case reports

Tracheopathia and tracheobronchopathia osteochondroplastica refer to idiopathic, non-malignant disease of large airways featured by sub-mucosal cartilaginous to osseous nodules overlying the cartilaginous rings, which may be focal or diffuse. We report two cases, one having tracheopathia osteochondroplastica and other having tracheobronchopathia osteochondroplastica. It is generally an overlooked diagnosis due to lack of familiarity among the clinicians. Our aim to present these cases is to avoid under-diagnosis/misdiagnosis whenever such a condition is encountered in daily practice.

Smokers with emphysema and small airway disease on computed tomography have lower bone density.

Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=−1.27, P=0.02 and b=−0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures.