Spectrum of Smoking-related Lung Diseases Imaging Review and Update Pdf

LEARNING OBJECTIVES

After reading this article and taking the test, the reader will be able to:

•.	Describe the spectrum of radiologic findings in smoking-related interstitial lung diseases with accent on the high-resolution CT findings.
•.	Listing the corresponding clinical features, pulmonary part exam results, and histopathologic findings.
•.	Hash out the evolving relationship between smoking and interstitial lung illness.

Introduction

Interstitial lung diseases (ILDs) are a heterogeneous group of disorders of known or unknown etiology, characterized by dyspnea, lengthened parenchymal lung abnormalities, restrictive pulmonary function, and impaired gas exchange (^,1).

Cigarette smoking is related to the development of several ILDs, including respiratory bronchiolitis ILD (RB-ILD), desquamative interstitial pneumonitis (DIP), pulmonary Langerhans cell histiocytosis (PLCH), and idiopathic pulmonary fibrosis (IPF) (^,Table 1). The smoking-related ILDs (SR-ILDs) are overlapping clinicopathologic entities that frequently coexist in the same patient. The contempo refinement of the classification of the idiopathic interstitial pneumonias (IIPs) and the increasing use of high-resolution computed tomography (CT) to narrate the ILDs (^,1,^,2) have lead to increased recognition and understanding of the SR-ILDs.

In this article, we hash out and illustrate the clinical features, high-resolution CT findings, and pathologic findings of the SR-ILDs. The diagnostic approach to patients with SR-ILD is discussed, emphasizing the need for integration of the radiologic-clinical-pathologic data in order to accomplish an accurate diagnosis.

Respiratory Bronchiolitis ILD

Respiratory bronchiolitis is a histopathologic lesion establish in the lungs of well-nigh all cigarette smokers. It is usually asymptomatic and of niggling clinical significance (^,3). Much less often, patients who are heavy smokers develop RB-ILD, a clinicopathologic entity characterized by pulmonary symptoms, abnormal pulmonary office test (PFT) results, and imaging abnormalities, with respiratory bronchiolitis being the histologic lesion at surgical lung biopsy (^,4).

Epidemiologic and Clinical Features

RB-ILD commonly affects electric current smokers 30–forty years of age with a 30 pack-year or greater history of cigarette smoking. There is a slight male predominance. Mild cough and dyspnea are the most common presenting symptoms. Inspiratory crackles are present in one-half of patients, and digital clubbing is rare (^,5). PFT results may be normal or show a mixed obstructive-restrictive pattern with reduced diffusing chapters (^,5).

Radiologic Findings

Chest radiographs oft appear normal, but they commonly show nonspecific thickening of the key and peripheral bronchial walls as fine bilateral reticulonodular opacities, typically upper lung or lengthened in distribution. The loftier-resolution CT findings are summarized in ^,Table 2.

The nigh common high-resolution CT findings in RB-ILD are centrilobular nodules, ground-drinking glass opacities, and thickening of the bronchial walls, which predominate in the upper lobes (^,Fig 1a^,). Upper lobe emphysema is also commonly present. A small percentage of patients have a reticular pattern due to fibrosis in the absenteeism of honeycombing and traction bronchiectasis (^,6–^,8). The differential diagnosis of RB-ILD includes acute hypersensitivity pneumonitis, DIP, and nonspecific interstitial pneumonitis (NSIP).

Figure 1a.  RB-ILD in a 32-year-onetime homo with a 17 pack-year history of smoking who presented with a cough, restrictive PFT results, and reduced diffusion capacity. (a) Loftier-resolution CT image obtained through the upper lungs shows bilateral centrilobular ground-glass nodules (arrow). (b) Photomicrograph of a surgical lung biopsy specimen shows a bronchiolocentric collection of pigmented macrophages (arrow).

Figure 1b.  RB-ILD in a 32-year-old homo with a 17 pack-year history of smoking who presented with a cough, restrictive PFT results, and reduced diffusion capacity. (a) Loftier-resolution CT image obtained through the upper lungs shows bilateral centrilobular ground-glass nodules (pointer). (b) Photomicrograph of a surgical lung biopsy specimen shows a bronchiolocentric drove of pigmented macrophages (arrow).

Histopathologic Findings

RB-ILD is characterized past pigmented macrophages and balmy interstitial inflammatory changes centering on respiratory bronchioles and neighboring alveoli (^{, ,}Fig 1b). The alveolar septa in the peribronchial regions may be mildly thickened just without significant fibrosis (^,4,^,9).

Handling and Outcome

Patients with RB-ILD generally take a proficient prognosis. The condition of most patients remains stable or improves, and no deaths have been attributed to RB-ILD, to our knowledge. Progressive fibrotic lung disease does not occur. Smoking cessation is the about important handling of RB-ILD. Corticosteroids have piffling part in most cases, although beneficial results have been reported in anecdotal symptomatic cases (^,5).

Desquamative Interstitial Pneumonitis

Although the term desquamative interstitial pneumonitis has been retained in the consensus classification of IIPs, information technology is considered a misnomer, every bit the predominant pathologic feature is the intraalveolar accumulation of pigmented macrophages and non desquamation of epithelial cells every bit previously thought. The condition represents the end spectrum of RB-ILD with similar pathologic findings and an near changeless association with smoking.

Epidemiologic and Clinical Features

DIP is an uncommon form of IIP that primarily affects cigarette smokers in their quaternary or 5th decades. Males are affected nearly twice equally often as females. Approximately 90% of patients with DIP are smokers. DIP can occasionally be seen in nonsmokers in clan with systemic disorders, infections, and exposure to occupational or environmental agents or drugs (^,9–^,11). Dyspnea and dry out cough are the most common presenting symptoms, and the onset is normally insidious. Inspiratory crackles are heard in threescore% of patients, and digital clubbing occurs in nearly half of patients (^,five). The most common and striking PFT abnormality is marked reduction in diffusing chapters, with reductions of l% or more being common (^,5). Restrictive defects are also common. Patients with avant-garde illness may have hypoxemia at rest or with exertion.

Radiologic Findings

Breast 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. The loftier-resolution CT findings of DIP are summarized in ^,Tabular array 3. The predominant abnormality at high-resolution CT in patients with DIP is ground-glass opacity, which may be peripheral, patchy, or diffuse in distribution (^,8,^,12). A peripheral subpleural and basal predominance of ground-glass opacity is most commonly seen (^,Fig 2a^{, ,}–^,2d^,). Honeycombing is uncommon. Coexistent emphysema may be present. At follow-up high-resolution CT of patients receiving handling, the ground-glass opacity may evidence partial or complete resolution (^,thirteen,^,fourteen) (^,Fig 3a^,–^,3c^,). Pocket-sized cystic spaces may develop inside the areas of footing-glass opacity (^{, ,}Fig 2b^{, , ,}), although progression to reticular aberration and honeycombing is unusual. The differential diagnosis includes RB-ILD, hypersensitivity pneumonitis, NSIP, and singular infections such as Pneumocystis carinii pneumonia.

Effigy 2a.  DIP and emphysema in a 48-year-quondam human with a thirty pack-twelvemonth history of smoking who presented with a coughing, gradually increasing shortness of breath, and mild restriction at pulmonary office testing, with diffusing chapters of the lung for carbon monoxide (Dlco) 50% of the predicted. (a) Loftier-resolution CT prototype obtained through the lower lungs shows bilateral diffuse basis-glass opacity (arrow). (b) High-resolution CT paradigm obtained through the mid lungs shows lengthened footing-glass opacity, peripheral reticulation, and small cysts (arrow). (c) High-resolution CT image obtained through the upper lungs shows paraseptal (arrow) and centrilobular emphysema. (d) Coronal reformatted paradigm shows the basilar predominant distribution of the footing-glass opacity and the apical emphysema. (e) Photomicrograph of a surgical lung biopsy specimen shows widespread intraalveolar accumulation of pigmented macrophages (arrows).

Effigy 2b.  DIP and emphysema in a 48-year-old human being with a 30 pack-yr history of smoking who presented with a cough, gradually increasing shortness of jiff, and balmy brake at pulmonary function testing, with diffusing capacity of the lung for carbon monoxide (Dlco) 50% of the predicted. (a) High-resolution CT epitome obtained through the lower lungs shows bilateral lengthened basis-glass opacity (pointer). (b) High-resolution CT paradigm obtained through the mid lungs shows diffuse ground-glass opacity, peripheral reticulation, and pocket-size cysts (arrow). (c) High-resolution CT paradigm obtained through the upper lungs shows paraseptal (arrow) and centrilobular emphysema. (d) Coronal reformatted image shows the basilar predominant distribution of the ground-glass opacity and the apical emphysema. (e) Photomicrograph of a surgical lung biopsy specimen shows widespread intraalveolar accumulation of pigmented macrophages (arrows).

Figure 2c.  DIP and emphysema in a 48-year-onetime homo with a 30 pack-year history of smoking who presented with a cough, gradually increasing shortness of breath, and balmy brake at pulmonary function testing, with diffusing chapters of the lung for carbon monoxide (Dlco) 50% of the predicted. (a) High-resolution CT image obtained through the lower lungs shows bilateral diffuse ground-drinking glass opacity (arrow). (b) High-resolution CT paradigm obtained through the mid lungs shows diffuse ground-drinking glass opacity, peripheral reticulation, and small cysts (arrow). (c) Loftier-resolution CT epitome obtained through the upper lungs shows paraseptal (arrow) and centrilobular emphysema. (d) Coronal reformatted image shows the basilar predominant distribution of the ground-glass opacity and the apical emphysema. (e) Photomicrograph of a surgical lung biopsy specimen shows widespread intraalveolar accumulation of pigmented macrophages (arrows).

Figure second.  DIP and emphysema in a 48-twelvemonth-old human with a 30 pack-year history of smoking who presented with a cough, gradually increasing shortness of jiff, and mild restriction at pulmonary part testing, with diffusing capacity of the lung for carbon monoxide (Dlco) 50% of the predicted. (a) High-resolution CT image obtained through the lower lungs shows bilateral diffuse basis-glass opacity (arrow). (b) High-resolution CT image obtained through the mid lungs shows diffuse ground-glass opacity, peripheral reticulation, and pocket-sized cysts (arrow). (c) Loftier-resolution CT image obtained through the upper lungs shows paraseptal (pointer) and centrilobular emphysema. (d) Coronal reformatted image shows the basilar predominant distribution of the ground-drinking glass opacity and the apical emphysema. (e) Photomicrograph of a surgical lung biopsy specimen shows widespread intraalveolar accumulation of pigmented macrophages (arrows).

Figure 2e.  DIP and emphysema in a 48-twelvemonth-sometime man with a xxx pack-yr history of smoking who presented with a coughing, gradually increasing shortness of breath, and mild brake at pulmonary office testing, with diffusing capacity of the lung for carbon monoxide (Dlco) l% of the predicted. (a) Loftier-resolution CT image obtained through the lower lungs shows bilateral diffuse ground-glass opacity (arrow). (b) High-resolution CT image obtained through the mid lungs shows diffuse footing-drinking glass opacity, peripheral reticulation, and small cysts (pointer). (c) Loftier-resolution CT epitome obtained through the upper lungs shows paraseptal (pointer) and centrilobular emphysema. (d) Coronal reformatted image shows the basilar predominant distribution of the ground-glass opacity and the apical emphysema. (e) Photomicrograph of a surgical lung biopsy specimen shows widespread intraalveolar accumulation of pigmented macrophages (arrows).

Effigy 3a.  DIP in a 50-year-old woman with a 25 pack-year history of smoking. Smoking continued after diagnosis. Corticosteroid therapy was started. (a) High-resolution CT image obtained through the right lower lung at initial diagnosis shows diffuse ground-glass opacity. (b) High-resolution CT epitome obtained through the right lower lung iii years later shows near-complete resolution of the ground-glass opacity. (c) High-resolution CT image obtained half-dozen months afterwards shows exacerbation of the DIP with new dumbo ground-glass opacity. Arrow = pocket-size right pneumothorax. (d) Photomicrograph of a surgical lung biopsy specimen shows diffuse interstitial chronic inflammation and pigmented macrophages within the alveoli and around bronchioles (arrows).

Figure 3b.  DIP in a 50-year-old woman with a 25 pack-year history of smoking. Smoking continued subsequently diagnosis. Corticosteroid therapy was started. (a) High-resolution CT image obtained through the right lower lung at initial diagnosis shows diffuse footing-glass opacity. (b) Loftier-resolution CT image obtained through the right lower lung 3 years later shows almost-complete resolution of the ground-drinking glass opacity. (c) High-resolution CT paradigm obtained 6 months later shows exacerbation of the DIP with new dense ground-drinking glass opacity. Arrow = pocket-size right pneumothorax. (d) Photomicrograph of a surgical lung biopsy specimen shows diffuse interstitial chronic inflammation and pigmented macrophages within the alveoli and around bronchioles (arrows).

Figure 3c.  DIP in a fifty-year-old woman with a 25 pack-year history of smoking. Smoking continued after diagnosis. Corticosteroid therapy was started. (a) High-resolution CT image obtained through the right lower lung at initial diagnosis shows diffuse ground-glass opacity. (b) Loftier-resolution CT image obtained through the right lower lung 3 years afterwards shows almost-consummate resolution of the ground-glass opacity. (c) High-resolution CT epitome obtained six months subsequently shows exacerbation of the DIP with new dense basis-glass opacity. Arrow = pocket-sized right pneumothorax. (d) Photomicrograph of a surgical lung biopsy specimen shows lengthened interstitial chronic inflammation and pigmented macrophages within the alveoli and around bronchioles (arrows).

Figure 3d.  DIP in a 50-year-erstwhile adult female with a 25 pack-twelvemonth history of smoking. Smoking continued after diagnosis. Corticosteroid therapy was started. (a) Loftier-resolution CT image obtained through the right lower lung at initial diagnosis shows lengthened footing-glass opacity. (b) High-resolution CT image obtained through the right lower lung iii years subsequently shows near-complete resolution of the ground-glass opacity. (c) Loftier-resolution CT image obtained 6 months later shows exacerbation of the DIP with new dense ground-drinking glass opacity. Pointer = small right pneumothorax. (d) Photomicrograph of a surgical lung biopsy specimen shows diffuse interstitial chronic inflammation and pigmented macrophages within the alveoli and around bronchioles (arrows).

Histopathologic Findings

The well-nigh striking finding in DIP is an increased number of pigmented macrophages evenly dispersed within the alveolar spaces (^,five) (^{, , , , ,}Figs 2e, ^{, , , ,}3d). Alveolar septa are thickened to a variable caste by lengthened fibrosis and balmy interstitial inflammation. The overall alveolar architecture is normally well maintained, and honeycombing is minimal or absent. The histologic features overlap with those of RB-ILD, and the key feature to differentiate the 2 disorders is the distribution and extent of lesions: bronchiolocentric in RB-ILD and diffuse in DIP.

Treatment and Outcome

Smoking cessation is the primary handling for DIP and may pb to illness regression. About patients with DIP receive oral corticosteroids. Although no randomized trials accept demonstrated the efficacy of this therapy, information technology is generally recommended for patients with significant symptoms, PFT abnormalities, and progressive disease. A college percent of patients with DIP answer to corticosteroid therapy than practise patients with UIP; approximately 2-thirds of DIP patients bear witness stabilization or improvement of symptoms, and complete recovery is possible. The response to corticosteroids is not uniform, equally approximately 25% of patients may go along to progress despite treatment (^,5). The function of cytotoxic and other immunosuppressive agents remains undefined. The 5- and ten-year survival rates are 95.2% and 69.6%, respectively (^,ten). Late relapse and recurrence in a transplanted lung have been reported (^,5).

Pulmonary Langerhans Jail cell Histiocytosis

The term Langerhans cell histiocytosis refers to a group of diseases of unknown etiology often recognized in childhood, in which Langerhans cell accumulations involve one or more trunk systems, including bone, lung, pituitary gland, mucous membranes, peel, lymph nodes, and liver. This illness is also referred to as histiocytosis X or eosinophilic granuloma. The term pulmonary Langerhans cell histiocytosis refers to disease in adults that affects the lung, commonly in isolation and less commonly in improver to other organ systems (^,15).

Epidemiologic and Clinical Features

Ninety percent to 100% of adults with PLCH are current or former smokers (^,xvi). The condition is uncommon, with a prevalence of 3.iv% in a series of 502 patients undergoing surgical lung biopsy for chronic diffuse infiltrative lung disease (^,17). The summit occurrence is at xx–40 years of age. Men and women are equally affected (^,xv). PLCH is more mutual in white patients. Up to 25% of patients are asymptomatic, with the illness discovered incidentally during radiologic studies. The near common presenting symptoms are nonproductive cough and dyspnea. Constitutional symptoms, such equally weight loss, fever, night sweats, and anorexia, occur in upwardly to one-third of patients. In 10% of patients, PLCH manifests as spontaneous pneumothorax.

PLCH in adults is usually isolated to the lungs. Extrapulmonary manifestations may occur in v%–fifteen% of patients and include bone lesions, diabetes insipidus, and pare lesions (^,15). Crackles and wheezes may occasionally be heard, and in avant-garde cases breath sounds are decreased. Clubbing is rare. At the time of presentation, PFTs show normal results or demonstrate mild obstructive, restrictive, or mixed abnormalities; all the same, the nearly frequent PFT abnormality is a reduction in diffusion capacity in threescore%–90% of patients (^,15). The prevalence and severity of pulmonary hypertension in advanced PLCH are much greater than in other chronic lung diseases and appear to exist at least in part independent of chronic hypoxemia and abnormal pulmonary mechanics. Intrinsic pulmonary vascular disease characterized by a severe diffuse pulmonary vasculopathy involving the pulmonary muscular arteries and interlobar veins is probable to be responsible (^,xviii).

Radiologic Findings

Chest radiographs demonstrate nodular or reticulonodular opacities predominantly in the upper lungs (^,nineteen). At that place is ordinarily sparing of the costophrenic angles. Lung volumes are preserved. As the disease advances, cystic changes and bullae appear in the upper lungs and lung volumes increase.

The loftier-resolution CT findings of PLCH are summarized in ^,Table 4. High-resolution CT is sensitive and specific for the diagnosis of PLCH, the characteristic finding being a combination of nodules and cysts predominating in the upper and mid lungs, sparing the bases (^,Fig iv). Early on in the disease, nodules with irregular borders predominate, mainly in a peribronchiolar distribution. As the disease evolves, thick- or sparse-walled cysts predominate and are often irregular (^,Figs 5a, ^,5b^{, ,}, ^,6a, ^,6b). Longitudinal studies with loftier-resolution CT testify that the solid nodules progress to cavitary nodules, then thick-walled cysts, and finally thin-walled cysts (^,twenty).

Figure 4.  Biopsy-proved PLCH with nodules and cysts in a smoker. High-resolution CT image obtained through the upper lungs shows a combination of nodules and cysts. Such a blueprint in a smoker makes the diagnosis almost sure. Some nodules are cavitating (pointer).

Figure 5a.  PLCH in a 42-year-quondam adult female with a xl pack-twelvemonth history of smoking who presented with a cough and dyspnea, a Dlco 45% of the predicted, and restrictive PFT results. (a, b) High-resolution CT images obtained through the upper (a) and lower (b) lungs show bilateral irregular cysts with an upper lung predominance. (c, d) Depression-ability (c) and high-ability (d) photomicrographs of a surgical lung biopsy specimen prove stellate peribronchiolar nodules (arrow in c) containing Langerhans cells (arrow in d).

Figure 5b.  PLCH in a 42-year-old woman with a 40 pack-year history of smoking who presented with a cough and dyspnea, a Dlco 45% of the predicted, and restrictive PFT results. (a, b) High-resolution CT images obtained through the upper (a) and lower (b) lungs bear witness bilateral irregular cysts with an upper lung predominance. (c, d) Low-power (c) and high-power (d) photomicrographs of a surgical lung biopsy specimen evidence stellate peribronchiolar nodules (pointer in c) containing Langerhans cells (arrow in d).

Figure 5c.  PLCH in a 42-year-old woman with a 40 pack-year history of smoking who presented with a cough and dyspnea, a Dlco 45% of the predicted, and restrictive PFT results. (a, b) High-resolution CT images obtained through the upper (a) and lower (b) lungs bear witness bilateral irregular cysts with an upper lung predominance. (c, d) Low-power (c) and high-power (d) photomicrographs of a surgical lung biopsy specimen show stellate peribronchiolar nodules (arrow in c) containing Langerhans cells (arrow in d).

Figure 5d.  PLCH in a 42-year-old woman with a 40 pack-yr history of smoking who presented with a cough and dyspnea, a Dlco 45% of the predicted, and restrictive PFT results. (a, b) High-resolution CT images obtained through the upper (a) and lower (b) lungs testify bilateral irregular cysts with an upper lung predominance. (c, d) Depression-power (c) and loftier-ability (d) photomicrographs of a surgical lung biopsy specimen evidence stellate peribronchiolar nodules (arrow in c) containing Langerhans cells (pointer in d).

Figure 6a.  PLCH with bone involvement in a 29-year-old male person smoker with rib pain and a coughing. (a) High-resolution CT epitome (bone window) shows a lucent cystic lesion in the right fifth rib (arrow). A biopsy specimen from the rib was diagnostic for eosinophilic granuloma, which was confirmed with immunohistochemical staining. (b) High-resolution CT epitome obtained through the upper lungs shows irregular cysts (arrow) and reticular opacities.

Figure 6b.  PLCH with bone involvement in a 29-year-old male smoker with rib pain and a cough. (a) High-resolution CT image (bone window) shows a clear-cut cystic lesion in the correct fifth rib (pointer). A biopsy specimen from the rib was diagnostic for eosinophilic granuloma, which was confirmed with immunohistochemical staining. (b) High-resolution CT paradigm obtained through the upper lungs shows irregular cysts (arrow) and reticular opacities.

In the appropriate clinical context, loftier-resolution CT findings are highly specific and obviate further testing (^,xv,^,21). In patients with only nodules at high-resolution CT, the differential diagnosis is extensive and includes sarcoidosis, silicosis, metastatic disease, and tuberculosis. The distribution in the upper and mid lungs and the centrilobular nature of the nodules in PLCH are helpful differentiating features. Cystic disease in PLCH should exist distinguished from lymphangioleiomyomatosis, emphysema, and IPF.

Histopathologic Findings

A cardinal histologic feature is the presence of cellular peribronchiolar nodules containing Langerhans cells and inflammatory cells in the early on stages (^,fifteen). Langerhans cells stain positive for S100, CD1a, and human being leukocyte antigen–DR at immunohistochemical assay. With time, at that place is a progression from cellular nodules to cellular and fibrotic nodules to entirely fibrotic nodules forming stellate peribronchiolar scars (^,22). At microscopic assay, there are discrete bronchiolocentric, stellate interstitial nodules separated by relatively normal or somewhat distorted lung tissue (^{, , ,}Fig 5c^,). At high power, Langerhans cells are distinguished by a moderate amount of low-cal eosinophilic cytoplasm and a single nucleus with an indented cerebriform outline and a finely dispersed chromatin pattern (^{, , , ,}Fig 5d). Varying degrees of respiratory bronchiolitis– or DIP-like changes are exceedingly common at histologic analysis in PLCH, away from the nodular lesions (^,23).

Treatment and Effect

Smoking cessation is essential and leads to stabilization of symptoms in well-nigh patients. In a substantial proportion, this may be the only intervention required (^,15). Corticosteroids are the mainstay of medical therapy for PLCH. Chemotherapeutic agents such as vinblastine, methotrexate, cyclophosphamide, etoposide, and cladribine have been used in patients with progressive disease unresponsive to corticosteroids or with multiorgan involvement (^,15). Lung transplantation is considered for patients with advanced PLCH associated with severe respiratory harm and express life expectancy.

The natural history is variable and unpredictable in an private patient (^,16). Approximately 50% of patients experience a favorable outcome with fractional or complete clearing of radiologic abnormalities and symptom resolution. In xxx%–forty% of patients, symptoms of variable severity persist; in ten%–20%, recurrent pneumothorax or progressive respiratory failure with cor pulmonale occurs. A few cases of recurrence despite smoking cessation take been reported.

Idiopathic Pulmonary Fibrosis

IPF is a distinctive pattern of chronic IIP of unknown cause limited to the lungs and associated with a surgical lung biopsy specimen showing UIP (^,1).

Human relationship of IPF to Smoking

A human relationship between cigarette smoking and IPF has been recognized for many years. Alveolar wall fibrosis in addition to coexistent emphysema was demonstrated at histopathologic analysis in early autopsy studies of smokers dying from emphysema (^,24). A loftier prevalence of current or old smokers is noted in series of IPF patients, varying from 41%–83% (^,5). In a multicenter case-command study, a history of smoking was associated with an increased risk of developing IPF, with an odds ratio of 1.6 (^,25). In a contempo meta-analysis of observational studies examining ecology and occupational gamble factors for IPF, statistically meaning increased risk for IPF was associated with cigarette smoking and exposures (^,26). The overall odds ratio for smoking as a risk cistron for IPF was 1.58. There is an independent stiff association between smoking and the development of familial interstitial pneumonia of various subtypes including UIP (odds ratio, 3.6; 95% confidence interval, one.3–9.eight) (^,27).

Recent work suggests that smoking may have a detrimental issue on IPF survival, with survival and severity-adjusted survival being college in nonsmokers than in former smokers or in a combined group of quondam and current smokers (^,28).

Epidemiologic and Clinical Features

IPF is the most common form of idiopathic ILD, manifesting in the 6th–7th decades with a slight male predominance. Clinical features include gradually progressing dyspnea, chronic coughing, and bibasilar inspiratory crackles (^,29). Digital clubbing is seen in approximately 2-thirds of patients. PFTs usually demonstrate a restrictive defect with reduced lung volumes and diffusing capacity.

Radiologic Findings

The typical chest radiograph in IPF shows bilateral basal and peripheral reticular opacities. Progressive fibrosis leads to a reduction in lung volumes and honeycombing. The high-resolution CT findings are summarized in ^,Table 5. Typical high-resolution CT features allowing confident diagnosis are irregular reticular opacities, traction bronchiectasis, and honeycombing in a basal peripheral and subpleural distribution (^,Fig seven^,). In item, honeycombing is a core finding in UIP that ordinarily facilitates distinction from other types of chronic IIPs at high-resolution CT.

Figure 7a.  Avant-garde IPF in a 69-twelvemonth-quondam onetime smoker with severe hypoxemia at residue. (a) CT image shows extensive honeycombing in the lower lungs. (b) High-resolution CT image obtained through the upper lungs shows peripheral honeycombing and reticulation (pointer).

Figure 7b.  Advanced IPF in a 69-twelvemonth-erstwhile former smoker with severe hypoxemia at residuum. (a) CT image shows extensive honeycombing in the lower lungs. (b) High-resolution CT image obtained through the upper lungs shows peripheral honeycombing and reticulation (pointer).

High-resolution CT has been shown to be a highly accurate tool for diagnosis of UIP, with a positive predictive value of 95%–100% (^,30). Withal, some cases of UIP are difficult to differentiate from fibrotic NSIP, which may exhibit honeycombing. The most useful finding when differentiating between NSIP and UIP at loftier-resolution CT is the greater extent of honeycombing in cases of UIP (^,31). The high-resolution CT differential diagnosis of IPF includes pulmonary fibrosis related to connective tissue disease and asbestosis, hypersensitivity pneumonitis, and drug toxicity.

Histopathologic Findings

Cardinal features of UIP are fibroblastic foci consisting of a cluster of fibroblasts and immature connective tissue within the pulmonary interstitium (^,1). Dense fibrosis causes remodeling of the lung architecture with honeycombing showing a basal and subpleural distribution. Temporal heterogeneity is a feature feature with fibrotic lesions of different stages in the same biopsy specimen (fibroblastic foci, mature fibrosis, and honeycombing). The histologic aberration is spatially heterogeneous, with patchy lung involvement and normal lung adjacent to severely fibrotic lung.

Handling and Outcome

The clinical course is gradual deterioration with a median survival of two.5–3.5 years (^,32). Treatment remains largely supportive; the response to steroids is poor, and no drug therapy has clearly demonstrated a survival benefit. A number of novel investigational agents are beingness studied, and lung transplantation is an option (^,33).

Combined Pulmonary Fibrosis and Emphysema

The combination of emphysema in the upper lobes and fibrosis in the lower lobes (CPFE) is being increasingly recognized every bit a distinct entity in smokers (^,34,^,35). Patients are almost exclusively men in their sixth and 7th decades. Lung volumes are relatively preserved despite markedly impaired diffusion chapters and hypoxemia during exercise. Honeycombing, reticular opacities, and traction bronchiectasis are the most frequent findings at high-resolution CT in the lower lungs, while the upper lungs exhibit paraseptal and centrilobular emphysema (^,Fig 8^{, , ,}).

Figure 8a.  CPFE in a 58-year-old male smoker with cough, dyspnea, and clubbing; a Dlco 35% of the predicted; and a family history of IPF (his female parent and a brother). (a) High-resolution CT image obtained through the upper lungs shows paraseptal (black arrow) and centrilobular (white arrow) emphysema. (b) High-resolution CT image obtained through the mid lungs shows peripheral honeycombing and reticulation (arrow). (c) CT paradigm shows traction bronchiectasis (arrow), reticular opacity, and ground-glass opacity in an expanse of the lower lung. (d) Sagittal reformatted image shows the upper lung apical distribution of the emphysema and the lower lung distribution of the fibrosis.

Figure 8b.  CPFE in a 58-year-onetime male smoker with coughing, dyspnea, and clubbing; a Dlco 35% of the predicted; and a family history of IPF (his mother and a brother). (a) High-resolution CT image obtained through the upper lungs shows paraseptal (black arrow) and centrilobular (white arrow) emphysema. (b) High-resolution CT image obtained through the mid lungs shows peripheral honeycombing and reticulation (arrow). (c) CT image shows traction bronchiectasis (arrow), reticular opacity, and ground-drinking glass opacity in an expanse of the lower lung. (d) Sagittal reformatted image shows the upper lung apical distribution of the emphysema and the lower lung distribution of the fibrosis.

Effigy 8c.  CPFE in a 58-yr-erstwhile male smoker with coughing, dyspnea, and clubbing; a Dlco 35% of the predicted; and a family history of IPF (his mother and a brother). (a) Loftier-resolution CT image obtained through the upper lungs shows paraseptal (black arrow) and centrilobular (white arrow) emphysema. (b) High-resolution CT epitome obtained through the mid lungs shows peripheral honeycombing and reticulation (pointer). (c) CT epitome shows traction bronchiectasis (arrow), reticular opacity, and ground-glass opacity in an area of the lower lung. (d) Sagittal reformatted image shows the upper lung upmost distribution of the emphysema and the lower lung distribution of the fibrosis.

Figure 8d.  CPFE in a 58-year-onetime male smoker with coughing, dyspnea, and clubbing; a Dlco 35% of the predicted; and a family unit history of IPF (his mother and a brother). (a) Loftier-resolution CT epitome obtained through the upper lungs shows paraseptal (black arrow) and centrilobular (white arrow) emphysema. (b) High-resolution CT image obtained through the mid lungs shows peripheral honeycombing and reticulation (arrow). (c) CT image shows traction bronchiectasis (arrow), reticular opacity, and footing-glass opacity in an surface area of the lower lung. (d) Sagittal reformatted image shows the upper lung apical distribution of the emphysema and the lower lung distribution of the fibrosis.

The high-resolution CT patterns are unremarkably typical of IPF, though in some series a greater prevalence of ground-drinking glass opacity with a pattern resembling fibrosing NSIP has been reported (^,35). Surgical lung biopsy usually reveals a pattern of UIP, though the coexistent presence of pigmented alveolar macrophages in a pattern resembling RB-ILD or DIP may exist found in areas. A histologic pattern of NSIP has as well been recognized in some patients with CPFE with ground-glass opacities in isolated cases (^,36) (^,Fig 9^,).

Figure 9a.  CPFE (NSIP pattern) in a 54-year-old man with an 80 pack-year history of smoking, resting hypoxemia, and a Dlco 19% of the predicted. (a) High-resolution CT image obtained through the upper lungs shows paraseptal emphysema (arrow). (b) Loftier-resolution CT image obtained through the lower lungs shows bilateral ground-glass opacity with septal thickening and traction bronchiectasis (pointer); there is no honeycombing.

Effigy 9b.  CPFE (NSIP pattern) in a 54-year-erstwhile man with an eighty pack-year history of smoking, resting hypoxemia, and a Dlco 19% of the predicted. (a) High-resolution CT image obtained through the upper lungs shows paraseptal emphysema (arrow). (b) High-resolution CT image obtained through the lower lungs shows bilateral footing-glass opacity with septal thickening and traction bronchiectasis (arrow); there is no honeycombing.

In some cases of CPFE, emphysema and fibrosis may co-occur in the same expanse of the lung (^,35). The resultant low-attenuation emphysematous foci may have apparent walls due to thickening of the adjacent interlobular septa. Such a high-resolution CT pattern may exist dislocated with other cystic lung affliction such every bit lymphangioleiomyomatosis and PLCH. Clinical correlation and attention to other imaging features such as nodules in PLCH and diffuse cystic change in lymphangioleiomyomatosis may be helpful.

At that place is a loftier prevalence of pulmonary hypertension in CPFE, and this is a disquisitional determinant of prognosis. Median survival is reported to be vi.i years, better than in patients with IPF alone but worse than expected for emphysema in the absence of fibrosis. Distinctive features of the CPFE syndrome are summarized in ^,Table six.

Overlap and Relationship between the Different SR-ILDs

The clinical, radiologic, and histologic features overlap among the dissimilar SR-ILDs. The overlap is most significant between RB-ILD and DIP. They may be different components of the aforementioned histopathologic disease spectrum, representing various degrees of severity of the same procedure caused by chronic smoking. Respiratory bronchiolitis or DIP changes at histologic analysis are very common in patients with PLCH, correlating with the cumulative exposure to cigarette smoke, and are oftentimes accompanied by significant ground-glass attenuation at loftier-resolution CT (^,23). Smokers who develop IPF often accept RB-ILD and DIP changes at loftier-resolution CT and histopathologic analysis (^,Fig x^{, , ,}), and patients with DIP may develop a loftier-resolution CT pattern of fibrotic NSIP over time (^,37). A combination of SR-ILD–related high-resolution CT findings, such as ground-glass opacities, cysts, micronodules, septal thickening, and honeycombing, tin can be seen in the same patient, confounding radiologic nomenclature into a discrete smoking-related entity.

Figure 10a.  Mixed design of UIP and DIP in a 53-year-erstwhile human being with a 30 pack-year history of smoking, restrictive PFT results, and a reduced Dlco. (a) High-resolution CT paradigm obtained through the mid lungs shows diffuse ground-drinking glass opacity with peripheral reticulation and mild honeycombing posteriorly (pointer). (b) CT image obtained through the lower lungs shows diffuse ground-glass opacity. (c, d) Photomicrographs of a surgical lung biopsy specimen bear witness temporally heterogeneous fibrosis (arrow in c) (UIP) and interstitial inflammation with intraalveolar macrophages (arrow in d) (DIP).

Effigy 10b.  Mixed pattern of UIP and DIP in a 53-year-old man with a thirty pack-yr history of smoking, restrictive PFT results, and a reduced Dlco. (a) Loftier-resolution CT image obtained through the mid lungs shows lengthened basis-glass opacity with peripheral reticulation and mild honeycombing posteriorly (arrow). (b) CT image obtained through the lower lungs shows diffuse ground-glass opacity. (c, d) Photomicrographs of a surgical lung biopsy specimen prove temporally heterogeneous fibrosis (arrow in c) (UIP) and interstitial inflammation with intraalveolar macrophages (pointer in d) (DIP).

Figure 10c.  Mixed pattern of UIP and DIP in a 53-twelvemonth-old man with a 30 pack-year history of smoking, restrictive PFT results, and a reduced Dlco. (a) High-resolution CT image obtained through the mid lungs shows diffuse ground-glass opacity with peripheral reticulation and mild honeycombing posteriorly (arrow). (b) CT prototype obtained through the lower lungs shows diffuse ground-drinking glass opacity. (c, d) Photomicrographs of a surgical lung biopsy specimen show temporally heterogeneous fibrosis (pointer in c) (UIP) and interstitial inflammation with intraalveolar macrophages (arrow in d) (DIP).

Effigy 10d.  Mixed blueprint of UIP and DIP in a 53-yr-old man with a 30 pack-yr history of smoking, restrictive PFT results, and a reduced Dlco. (a) High-resolution CT epitome obtained through the mid lungs shows diffuse ground-drinking glass opacity with peripheral reticulation and mild honeycombing posteriorly (pointer). (b) CT image obtained through the lower lungs shows diffuse footing-drinking glass opacity. (c, d) Photomicrographs of a surgical lung biopsy specimen show temporally heterogeneous fibrosis (pointer in c) (UIP) and interstitial inflammation with intraalveolar macrophages (arrow in d) (DIP).

Diagnostic Approach to Patients with SR-ILDs

An integrated clinical, radiologic, and pathologic arroyo to the diagnosis of SR-ILD is recommended, as with other lengthened parenchymal lung diseases (^,1). The diagnostic process begins with a clinical evaluation that includes history, physical exam, chest radiography, and pulmonary function tests. Loftier-resolution CT plays an integral role in evaluation. In the appropriate clinical context, the presence of typical changes at loftier-resolution CT, such as nodules and cysts in PLCH and honeycombing and emphysema in smoking-related IPF, renders the diagnosis well-nigh sure and may obviate further testing. Surgical lung biopsy is indicated when the findings at high-resolution CT are relatively nonspecific, as in RB-ILD and DIP, or when a confident definitive diagnosis is needed.

A final diagnosis of an SR-ILD and identification of the specific entity can exist made with certainty only afterward the pulmonologist, radiologist, and pathologist take reviewed all of the clinical, radiologic, and pathologic data. Distinction of SR-ILD from other forms of diffuse parenchymal lung disease and recognition of the specific pattern of SR-ILD, in particular the separation of RB-ILD, DIP, and PLCH from IPF, have important clinical implications. Smoking cessation is an of import component in the management of SR-ILD, though the natural history of SR-ILD and the influence of smoking on the clinical course of these patients accept not been fully delineated. Smoking cessation may pb to improvement in many patients with RB-ILD and full general stabilization or improvement in DIP and PLCH. In general, the prognosis for RB-ILD, DIP, and PLCH is significantly improve than that for IPF.

Conclusions

The variety of ILDs associated with cigarette smoking is wider than generally appreciated, and many forms frequently coexist. Although key loftier-resolution CT findings of SR-ILDs can exist recognized, mixed patterns of affliction associated with cigarette smoking may be confusing at high-resolution CT, peculiarly when combined with an interstitial pneumonitis such as NSIP. An integrated clinical, radiologic, and pathologic approach is necessary for authentic diagnosis of the SR-ILDs.

Table i. Smoking-related ILDs

Table 2. High-Resolution CT Findings of RB-ILD

Table 3. Loftier-Resolution CT Findings of DIP

Table iv. Loftier-Resolution CT Findings of PLCH

Table five. High-Resolution CT Findings of IPF

Tabular array 6. Distinctive Features of CPFE

See the commentary by Ketai following this commodity.

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Source: https://pubs.rsna.org/doi/10.1148/rg.285075223

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