Smoking related interstitial lung diseases

Smoking-related Interstitial Lung Diseases

The Never-Ending Story of Smoke

and Disease


Mostafa ElshazlyMD, FCCP,ERSD,

Professor of Pulmonary MedicineChairman of PVRU

Kasr ElAini School Of Medicine Cairo University


Cigarette smoke is a complex mixture of more

than 6,000 compounds and causes a variety of

pulmonary and systemic effects in humans .

Smoking remains the most preventable cause of

premature death and morbidity in the United

States and throughout the developed world .

Cigarette smoking is the major cause of lung

cancer, which in turn is the leading cause of

cancer deaths in both males and females in the

United States .









cancer, which in turn is the leading cause of cancer

deaths in both males and females in the United

States .









cancer, which in turn is the leading cause of

cancer deaths in both males and females in the

United States .


• Smoking-induced lung diseases constitute

a complex group of disorders, varying from

the well- known entity of chronic

obstructive pulmonary disease (COPD) to

the more recently described interstitial

lung diseases (ILDs) 1,2

1. Baumgarten Kbet al., Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1997;155:242–248.2. Heynemann LE, et al., RB,RB_ILD,and DIP : different entities or part of the spectrum of the same disease process? AJR Am J Roentgenol 1999;173:1617–1622.

• Smoking-related ILD is a term used to describe the relationship between

– RB-associated ILD (RB-ILD),

– Desquamative interstitial pneumonia (DIP), and

– Pulmonary Langerhans’ cell histiocytosis

(PLCH)

• as interstitial disorders that are

etiologically linked to cigarette smoking 1 .


Moon J, du Bois RM, Colby TV, Hansell DM, Nicholson AG. Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease. Thorax 1999; 54:1009–1014.

Copyright © American College of Chest Physicians. All rights reserved.

The Overlap Between Respiratory Bronchiolitis and Desquamative Interstitial Pneumonia in Pulmonary Langerhans Cell Histiocytosis*: High-Resolution CT, Histologic, and Functional Correlations

Chest. 2003;124(4):1199-1205. doi:10.1378/chest.124.4.1199

Nonproportional Venn diagram illustrating the spectrum of airways and interstitial injury associated with cigarette smoking. The larger outer circle represents the virtually universal occurrence of RB in smokers. Emphysema will develop in approximately 20% of these smokers during their lifetime. ILD will develop in a small proportion of smokers due to DIP or PLCH. In a significant proportion of those in whom DIP or PLCH develops (or overlaps of both), there is accompanying emphysema (as in the current series). which provides evidence that RBILD, DIP and PLCH form a spectrum of interstitial patterns of lung injury related to cigarette smoke .

• This direct causative role for smoking in the pathogenesis of these disorders is based on significant epidemiological data:– Consistent preponderance of smokers within

this population– Potential of disease remission upon smoking

cessation– the existence of similar lesions, namely

respiratory bronchiolitis, in healthy smokers without ILD, and

– the presence of a combination of these lesions in some affected smokers 1,2 .


1.Ryu JH, Colby TV, Hartman TE, et al. Smoking-related interstitial lung diseases: a concise review. Eur Respir J 2001; 17: 122–132. 20.Vassalo R, Ryu JH. Tobacco smoke-related diffuse lung diseases. Semin Respir Crit Care Med 2008; 29: 643–650.

• This direct causative role for smoking in the pathogenesis of these disorders is based on significant epidemiological data:– Consistent preponderance of smokers within

this population– Potential of disease remission upon smoking

cessation– Existence of similar lesions, Respiratory

Bronchiolitis, in healthy smokers without ILD, and

– The presence of a combination of these lesions in some affected smokers 1,2 .


1.Ryu JH, Colby TV, Hartman TE, et al. Smoking-related interstitial lung diseases: a concise review. Eur Respir J 2001; 17: 122–132. 20.Vassalo R, Ryu JH. Tobacco smoke-related diffuse lung diseases. Semin Respir Crit Care Med 2008; 29: 643–650.

• Pathogenesis



• Pathogenesis• Cigarette smoke can injure the

endothelial and the alveolar

epithelial cells by increasing

oxidative stress and enhancing

virus induced parenchymal

inflammation.

• Such injury could lead to

abnormal wound healing and

parenchymal fibrosis in

susceptible individualsSmoking-related Interstitial Lung

Diseases


• Pathogenesis• Cigarette smoke can injure the

endothelial and the alveolar

epithelial cells by increasing

oxidative stress and enhancing

virus induced parenchymal

inflammation.

• Such injury could lead to

abnormal wound healing and

parenchymal fibrosis in

susceptible individuals

Respiratory Bronchiolitis Associated

Interstitial Lung Disease (RB-ILD)

• Is a rare, mild inflammatory pulmonary disorder

that occurs almost exclusively in current or

former heavy smokers, usually between the third

and sixth decades, most likely with no gender

predilection.

Sieminska and Kuziemski: Respiratory bronchiolitisinterstitial lung disease. Orphanet Journal of Rare Diseases 2014 9:106.



• Epidemiology

• The prevalence and incidence of RB-ILD is

unknown and has remained difficult to assess for

many years.

• In several earlier case series, the incidence of RB-

ILD & DIP, 10%–17% of the study samples 1,2 .

• RB-ILD was recorded separately in only two of

these case series, and accounted for 2% and 13%

of cases 3.

1. Bjoraker JA, et al., Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998, 157:199–203. 2.Nicholson AG, et al.,: The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 2000, 162:2213–2217. 3. Flaherty KR, et al., Clinical significance of histological classification of idiopathic interstitial pneumonia. Eur Respir J 2002, 19:275–83.



• Epidemiology

• In KSA register of newly diagnosed ILD cases, RB-

ILD cases accounted for 5.5% of all types of IIPs 1

.

• A German pathology review of ILD cases revealed

9.5% of RB-ILD cases among all types of IIPs 2 .

1.Alhamad EH: Interstitial lung diseases in Saudi Arabia: a single-center study. Ann Thorac Med 2013, 8:33–7.2. Theegarten D, Müller HM, Bonella F, Wohlschlaeger J, Costabel U: Diagnostic approach to interstitial pneumonias in a single centre: report on 88 cases. Diagn Pathol 2012, 7:160–171.


Interstitial Lung Disease (RB-ILD)• Clinical description

• Insidious onset of

– Exertional dyspnea,

– Symptomatic wheezing, and

– Persistent cough, which may be non-productive.

• Bibasilar end-inspiratory crackles are the most

common signs.

Portnoy J, Veraldi KL, Schwarz MI, Cool CD, Curran-Everett D, Cherniack RM, King TE Jr, Brown KK: Respiratory bronchiolitis-interstitial lung disease:long-term outcome. Chest 2007, 131:664–671.


Interstitial Lung Disease (RB-ILD)• Physiologic changes

• Obstructive pattern was the most common

pulmonary function defect (47%)

• Pure restriction or mixed defects were less

common (31% and 9%, respectively)

• 13% of patients had normal spirometry data .

Portnoy J, Veraldi KL, Schwarz MI, Cool CD, Curran-Everett D, Cherniack RM, King TE Jr, Brown KK: Respiratory bronchiolitis-interstitial lung disease:long-term outcome. Chest 2007, 131:664–671.


Interstitial Lung Disease (RB-ILD)• Physiologic changes

• Patients with minimal symptoms usually

reveal a mild to moderate decrease in DLco.

• Patients with more severe symptoms, both

airway obstruction and restriction or

occasionally an isolated increase in RV may

be found .Myers JL, Veal CF Jr, Shin MS, Katzenstein AL: Respiratory bronchiolitis causing interstitial lung disease: a clinicopathological study of six cases. Am Rev Respir Dis 1987, 135:880–4.


Interstitial Lung Disease (RB-ILD)• Radiographic findings

• Radiographic findings are usually relatively

subtle.

• Normal chest radiographs ( 20% to 28%) .

• Fine reticulonodular interstitial opacities, which

are diffuse or are predominant in basal lung

areas . 1, 2

Park JS, et al.,: Respiratory bronchiolitis-associated interstitial lung disease: radiologic features with clinical and pathologic correlation. J Comput Assist Tomogr 2002, 26:13–20.Heyneman LE, et al.,: RB,RB-ILD,DIP different entities or part of the spectrum of the same disease process. Am J Roentgenol 1999, 173:1617–22.


Interstitial Lung Disease (RB-ILD)• High-Resolution CT Findings of RB-ILD

– Centrilobular nodular opacities– Patchy ground-glass opacity– Bronchial wall thickening– Upper lobe predominance– Associated centrilobular emphysema– Air trapping at expiration– Findings of fibrosis absent

Park JS, et al.,: Respiratory bronchiolitis-associated interstitial lung disease: radiologic features with clinical and pathologic correlation. J Comput Assist Tomogr 2002, 26:13–20.Anil K. Attili, et al., Smoking-related Interstitial Lung Disease: Radiologic-Clinical-Pathologic Correlation. RadioGraphics 2008; 28:1383–1398



– Centrilobular nodular opacities– Patchy ground-glass opacity– Bronchial wall thickening– Upper lobe predominance– Associated centrilobular emphysema– Air trapping at expiration– Findings of fibrosis absent



– Patchy ground-glass opacity– Bronchial wall thickening



– Upper lobe predominance



– Associated centrilobular emphysema



– Associated centrilobular emphysema

HRCT image of the upper lung lobes shows centrilobular nodules (white arrows), patchy ground-glass opacities (black arrow), and mild coexisting centrilobular emphysema (arrowhead).


Interstitial Lung Disease (RB-ILD)Histopathologic Findings Pigmented

macrophages in a terminal bronchiole and the adjacent alveoli (arrows), and

Moderate Peribronchiolar inflammation and fibrosis (arrowhead) are present.


Interstitial Lung Disease (RB-ILD)• Bronchoalveolar lavage

– An increased total number of cells with a

normal cellular differential analysis .

– or an increase in the percentage of

macrophages.

– A modest increase in neutrophils may also be

present.

Hunninghake GW, Crystal RG: Cigarette smoking and lung destruction: accumulation of neutrophils in the lungs of cigarette smokers. Am Rev Respir Dis 1983, 128:833–838.


Interstitial Lung Disease (RB-ILD)• Diagnosis

• It is increasingly accepted that a diagnosis of RB-

ILD is secure when based upon

– Typical HRCT findings (ground-glass opacities and

centrilobular nodules)

– In a current smoker, especially when

– BAL findings (the presence of smokers’ macrophages

and the absence of lymphocytosis) are also compatible.


Interstitial Lung Disease (RB-ILD)• Management and disease course

• Smoking cessation is considered the most

important factor in the management of RB-ILD.

• It is also unclear whether patients with RB-ILD

benefit from corticosteroid therapy with regard to

the natural history of the disease.


Interstitial Lung Disease (RB-ILD)• Management and disease course• The course of RB-ILD is heterogeneous, often with

no functional improvement and with disease progression despite smoking cessation and treatment 1,2,3 .

• Clinical worsening was common, as well as worsening of spirometry results and gas exchange, regardless of smoking status and treatment ordered, including corticosteroids 3.

• RB-ILD is now less commonly regarded as a benign entity.

Moon J, et al.,: Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease. Thorax 1999, 54:1009–14. 2. Ryu JH, et al.,:Desquamative interstitial pneumonia and respiratory bronchiolitis–associated interstitial lung disease. Chest 2005, 127:178–184.3. Portnoy J, Veraldi KL, Schwarz MI, Cool CD, Curran-Everett D, Cherniack RM, King TE Jr, Brown KK: Respiratory bronchiolitis-interstitial lung disease: long-term outcome. Chest 2007, 131:664–671.

Desquamative Interstitial Pneumonia (DIP)


It was originally defined by Liebow et al. in 1965 1.

In the following 2 decades it was considered as the

putative early stage of the usual interstitial

pneumonia (UIP) 2

Initially, it was believed that its histological feature

was the desquamation of epithelial cells, but then it

was recognized that the presence of intra-alveolar

macrophages was due to an alveolar filling process 3.1.Liebow AA, et al.,. Desquamative interstitial pneumonia. Am J Med 1965; 39: 369–404. 2.Tubbs RR, et al. Desquamative interstitial pneumonitis. Cellular phase of fibrosing alveolitis. Chest 1977; 72: 159–165.3. Ryu JH, et al. Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease. Chest 2005; 127: 178–184.


DIP is associated to tobacco in nearly 80–90% of patients 1 but, could also be associated to many drugs 2

systemic disorders 3

environmental exposures 4

and infections 4

In addition, it also has been described in children .

1.ATS-ERS. International multidisciplinary consensus. Classification of the IIPs. Am J Respir Crit Care Med 2002;165: 277–30. 2. Corrin B, Price AB. Electron microscopic studies in desquamative interstitial pneumonia associated with asbestos. Thorax 1972; 27:324–331. 3.Abraham JL, Hertzberg MA. Inorganic particles associated with desquamative interstitial pneumonia. Chest 1981; 80: 67–70. 4. Craig JP, Wells AU, Doffman S, et al. Desquamative interstitial pneumonia, respiratory bronchiolitis and their relationship to smoking. Histopathol 2004; 45: 275–282


The average age at the onset of symptoms is about 40 years 1

Male-Female ratio of 2 : 1 2

Clinical presentation of DIP is Insidious and is characterized by Progressive dyspnea and dry cough. Inspiratory crackles are present in 60% and Digital clubbing in 50% of patients 3.

1.ATS-ERS. International multidisciplinary consensus. Classification of the IIPs. Am J Respir Crit Care Med 2002;165: 277–30. 2. Corrin B, Price AB. Electron microscopic studies in desquamative interstitial pneumonia associated with asbestos. Thorax 1972; 27:324–331. 3.Abraham JL, Hertzberg MA. Inorganic particles associated with desquamative interstitial pneumonia. Chest 1981; 80: 67–70.


Physiologic changes

The most common and striking PFT abnormality is

marked reduction in diffusing capacity, with

reductions of 50% or more being common 1 .

Restrictive defects are also common.

Patients with advanced disease may have

hypoxemia at rest or with exertion.

Ryu JH, Myers JL, Capizzi SA, Douglas WW, Vassallo R, Decker PA. Desquamative interstitial pneumonia and respiratory bronchiolitisassociated interstitial lung disease. Chest 2005;127:178–184.


Radiologic Findings

Chest radiographs are insensitive for detection

of DIP and are reported to be normal in 3%–

22% of biopsy-proved cases 1 .

The radiologic patterns are nonspecific and

include patchy ground glass opacities with a

lower lung and peripheral predominance.

Hartman TE, Primack SL, Swensen SJ, Hansell D, McGuinness G,Mu¨ ller NL. Desquamative interstitial pneumonia: thin-section CT findings in 22 patients. Radiology 1993;187:787–790.


Radiologic Findings

Chest radiograph of a patient with desquamative interstitial pneumonia (DIP) showing bilateral

interstitial infiltrates involving mainly the lower lung zones. Mild, localized areas of fibrosis cause

a reticular pattern.


High-Resolution CT Findings

Bilateral patchy ground-glass opacity

Reticular opacities

Subpleural and basal predominance

Honeycombing uncommon

Associated centrilobular emphysema

Anil K. Attili, et al., Smoking-related Interstitial Lung Disease: Radiologic-Clinical-Pathologic Correlation. RadioGraphics 2008; 28:1383–1398



Bilateral patcReticular opacities




hy ground-glass opacity


HistologicallyThe main characteristic of DIP is the presence

of pigmented macrophages within the alveolar spaces that stain in a nonspecific fashion with PAS-diastase [8].

Minimal to moderate alveolar septal widening usually accompanies the air-spaces changes.

Honeycombing is rare [16, 32].


Macrophage accumulations within most of the distal air spaces. The alveolar septa are thickened by a sparse inflammatory infiltrate.The intraluminal macrophages in DIP frequently contain dusty brown pigment


• Treatment and Outcome– Smoking cessation is the primary treatment

for DIP and may lead to disease regression– Oral corticosteroids is generally

recommended for patients with• Significant symptoms,• PFT abnormalities, and• Progressive disease.

– The response to corticosteroids is not uniform


• Treatment and Outcome• The 5- and 10-yr survival rates are 95.2 and

69.6%, respectively, for patients with DIP 1 . • Nevertheless, DIP progresses in some cases and a

small number of patients have a poor outcome 2 .• Lung transplantation has been performed

successfully in patients with end-stage disease; however, disease recurrence in the transplanted lung has been reported 3 .

1.Carrington CB et al., . Natural history and treated course of usual and desquamative interstitial pneumonia. N Engl J Med 1978;298:801–809. 2. Hartman TE,et al., Disease progression in usual interstitial pneumonia compared with desquamative interstitial pneumonia: assessment with serial CT. Chest 1996;110:378–382. 3. Barberis M, Harari S, Tironi A, Lambertico P. Recurrence of primary disease in a single lung transplant recipient. Transplant Proc 1992;24: 2660–2662.

Pulmonary langerhans cell histiocytosis

The histiocytic disorders are rare diseases characterized by abnormal infiltration of certain organs by cells derived from monocyte/macrophage or dendritic cell lineage .

Langerhans Cell Histocytosis (LCH) is a specific type of histocytic syndrome characterized by infiltration of tissues with a specific dendritic cell, the Langerhans cell .

Favara BE, et al: Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol 1997, 29(3):157-166.


Pulmonary Langerhans cell

histiocytosis refers to disease in adults

that affects the lung, usually in isolation

and less commonly in addition to other

organ systems .

Vassallo R, Ryu JH, Colby TV, Hartman T, Limper AH. Pulmonary Langerhans’-cell histiocytosis. N Engl J Med 2000;342:1969–1978.


Epidemiology and demographic characteristicsPLCH is a rare disease which occurs almost

exclusively in smokers 1,2 .Estimated incidence 4-5% of all DLD biopsies

3 .Affects young adults between the ages of 20 to

40 years1. No gender predilection 1,4.

1.Vassallo R, et al.,: Clinical outcomes of pulmonary Langerhans’-cell histiocytosis in adults. N Engl J Med 2002, 346(7):484-490. 2. Arico M, et al.,: Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer 2003, 39(16):2341-2348. 3. Gaensler EA, Carrington CB: Open biopsy for chronic diffuse infiltrative lung disease: clinical, roentgenographic, and physiological correlations in 502 patients. Ann Thorac Surg 1980, 30(5):411-426. 4. Travis WD, et al.,: Pulmonary Langerhans cell granulomatosis (histiocytosis X). A clinicopathologic study of 48 cases. Am J Surg Pathol 1993, 17(10):971-986

Pathogenesis

• It is possible that smokers with PLCH develop

an amplified inflammatory response induced by

tobacco smoke (and possibly other factors) that

induces activation of multiple cell types in the

lung, including epithelial and immune cells,

resulting in a vicious cycle of inflammation,

tissue injury and tissue remodeling

Pathogenesis

• Whether failure of endogenous anti-

inflammatory mechanisms or additional

exogenous insults like viral infections have

a role in promoting smoking induced PLCH

is unknown, and continues to be an

important area of investigation.

The primary event in the pathogenesis probably involves cigarette smoke-induced recruitment and activation of LCs to the small airways, a process that may result from a variety of potential mechanisms.

Pathogenesis

Cigarette smoke activates epithelial cells and macrophages toproduce cytokines and chemokines Cigarette smoke may also directly activateLCs.Langerhans cells conditioned by cigarette smokemay inappropriately recognize autontigens in the lungs and activate adaptive T cell responses that secondarily mediate injury in airway tissues

Pathogenesis

Chronic inflammation and cytokine production(particularly TGF-b) may promote local fibroblast activation and airway-centered fibrosis.

The combination of airway centered inflammation and tissue remodeling promote dilatation of structures distal to the inflamed small airways and cystic formation.

Pathogenesis


Clinical Features

Ninety percent to 100% of adults with PLCH

are current or former smokers 1.

Prevalence of 3.4%.

Peak occurrence is at 20–40 years of age.

Men and women are equally affected 2.

1.Braier J, et al.,: Outcome in children with pulmonary Langerhans cell Histiocytosis. Pediatric blood & cancer 2004, 43(7):765-769. 2. Seely JM, et al.,: Pulmonary Langerhans Cell Histiocytosis: A Comparative Study of Computed Tomography in Children and Adults. Journal of thoracic imaging 2010.


Clinical Features

– Up to 25% of patients are asymptomatic.

– Nonproductive cough and dyspnea.

– Weight loss, fever, night sweats, and anorexia,

(33%).

– Spontaneous pneumothorax (10%)

– Crackles and wheezes may occasionally be heard,

and in advanced cases breath sounds are decreased.1.Braier J, et al.,: Outcome in children with pulmonary Langerhans cell Histiocytosis. Pediatric blood & cancer 2004, 43(7):765-769. 2. Seely JM, et al.,: Pulmonary Langerhans Cell Histiocytosis: A Comparative Study of Computed Tomography in Children and Adults. Journal of thoracic imaging 2010.


Pulmonary function and echocardiographic findings

PFT findings are variable depending upon the course of the disease and prevalent anatomical lesions .

Up to 20% of patients have normal PFT. 70% of patients have low DLCO, which is the most

common physiologic abnormality observed. A restrictive pattern (earlier stages) Obstructive pattern (predominant as disease

progresses) . Pulmonary Hypertension in advanced PLCH are much

greater than in other chronic lung diseases.

Vassallo R, Ryu JH, Schroeder DR, Decker PA, Limper AH: Clinical outcomes of pulmonary Langerhans’-cell histiocytosis in adults. N Engl J Med 2002, 346(7):484-490.








Vassallo R, Ryu JH, Schroeder DR, Decker PA, Limper AH: Clinical outcomes of pulmonary Langerhans’-cell histiocytosis in adults. N Engl J Med 2002, 346(7):484-490.


Radiographic findings

• CXR is almost always abnormal, although the

findings may be subtle and easy to overlook .

• Reticulonodular infiltrates are predominant in

early disease whereas cystic lesions are more

dominant in advanced disease

• Predominantly involving upper and middle lobes

with relative sparing of lung bases.


Radiographic findings


HRCT Findings of PLCH• Thin-walled cysts, some confluent or with bizarre

shapes.• Thick-walled cysts.• Nodules, usually 1–5 mm, centrilobular or

peribronchial, may be cavitary, and seen in association with cysts.

• Progression from three to two to one .• Upper lobe predominance of nodules and cysts,

costophrenic angles spared.• Fine reticular opacities.• Ground-glass opacities.


HRCT Findings of PLCH• Thin-walled cysts, some confluent or with bizarre

shapes


HRCT Findings of PLCH• Thick-walled cysts.


HRCT Findings of PLCH• Nodules, usually 1–5 mm, centrilobular or

peribronchial, may be cavitary, and seen in association with cysts


HRCT Findings of PLCH• Upper lobe predominance of nodules and cysts,

costophrenic angles spared.• Fine reticular opacities.• Ground-glass opacities.


HRCT Findings of PLCH

• Upper lobe predominance of nodules and cysts, costophrenic angles spared.

• Fine reticular opacities.• Ground-glass opacities.


Bronchoalveolar lavage (BAL)

BAL should be performed in all patients as the

detection of > 3% CD1a-positive cells

(Langerhans’ cells) in the appropriate clinical

context (supported by consistent chest HRCT

findings) is highly suggestive of PLCH 1,2 .

1.Auerswald U, Barth J, Magnussen H: Value of CD-1-positive cells in bronchoalveolar lavage fluid for the diagnosis of pulmonary histiocytosis X. Lung 1991, 169(6):305-309.2. Chollet S, Soler P, Dournovo P, Richard MS, Ferrans VJ, Basset F: Diagnosis of pulmonary histiocytosis × by immunodetection of Langerhans cells in bronchoalveolar lavage fluid. Am J Pathol 1984, 115(2):225-232.


Histopathologic Findings Lung biopsy is necessary for a definitive

diagnosis

• A key histologic feature is the presence of cellular

peribronchiolar nodules containing Langerhans

cells and inflammatory cells in the early stages

(15).

• LCs stain positive for S100, CD1a, and HLA–DR at

immunohistochemical analysis.


Histopathologic Findings Lung biopsy is necessary for a definitive

diagnosis

• A key histologic feature is the presence of cellular

peribronchiolar nodules containing Langerhans

cells and inflammatory cells in the early stages 1.

• LCs stain positive for S100, CD1a, and HLA–DR at

immunohistochemical analysis.

Suri et al.: Pulmonary langerhans cell histiocytosis. Orphanet Journal of Rare Diseases 2012 7:16.

a low-power microscopic picture with nodular airway-centered lesions

showing microcystic change

High-power shows diffuse infiltration of lung tissue with Langerhans cells showing vesicular nuclear chromatin, irregular nuclear contour and moderate amount of pale cytoplasm devoid of phagocytosed material. Many eosinophils are also intermixed among Langerhans cells

High-power photomicrographs of a surgical lung biopsy specimen Staining is both

nuclear and cytoplasmic with S100.


Treatment and Outcome– Smoking cessation is essential and leads to

stabilization of symptoms in most patients.

– Corticosteroids are the mainstay of medical therapy for PLCH.

– Lung transplantation is considered for patients with advanced PLCH associated with severe respiratory impairment and limited life expectancy.




– Pharmacotherapy with immunosuppressive medication should be considered for • Patients with severe disease, or

• Patients in whom progressive decline in lung function occurs.



Outcomes and prognosis– The course of PLCH in adults is variable and

unpredictable, ranging from asymptomatic to progressive debilitating disease that leads to respiratory failure and death over a period of few years.

– Several factors have been associated with poor outcome including • Extremes of age, Prolonged constitutional symptoms,• Multi-organ involvement,• Extensive cysts and honeycombing on the radiograph,• Severely DLCO & obstructive physiology• prolong treatment with steroid therapy and• associated pulmonary hypertension


Outcomes and prognosis– The course of PLCH in adults is variable and

unpredictable, ranging from asymptomatic to progressive debilitating disease that leads to respiratory failure and death over a period of few years.

– Several factors have been associated with poor outcome including • Extremes of age, Prolonged constitutional symptoms,• Multi-organ involvement,• Extensive cysts and honeycombing on the radiograph,• Severely DLCO & obstructive physiology• Prolong treatment with steroid therapy and• Associated pulmonary hypertension.

Conclusions• The variety of ILDs associated with cigarette

smoking is wider than generally appreciated, and

many forms often coexist.

• Although key high-resolution CT findings of SR-ILDs

can be recognized, mixed patterns of disease

associated with cigarette smoking may be confusing.

• An integrated clinical, radiologic, and pathologic

approach is necessary for accurate diagnosis of the

SR-ILDs.

ConclusionsRB-ILD

DIP

PLCH

AEP

SRIF

CPFE

Smoking related interstitial lung diseases

Health & Medicine

Transcript of Smoking related interstitial lung diseases