1000-2000 5 ьшò

Bronchoscopy

–Bronchoalveolar lavage (BAL) cellular analysis studies may be useful in distinguishing subtypes (including sarcoidosis, hypersensitivity pneumonitis, cancer). If performed, the BALtarget site should be chosen based on the HRCT finding.

–Bronchoscopic transbronchial lung biopsy may help diagnose sarcoidosis

and, on occasion, is sufficiently supportive of other ILD diagnoses.

Thoracoscopic surgery for lung biopsy has the greatest diagnostic specificity for ILDs but is less frequently used given improved specificity of HRCT; may be indicated if a diagnosis cannot be determined from transbronchial biopsy or HRCT

Test Interpretation

Diagnostic classifications of IIPs are based on histopathologic patterns seen on lung biopsy.

Major histologies include an inflammation and fibrotic and granulomatous patterns.

Characteristic changes on HRCT may help to distinguish between the following subtypes:

–Reticulonodular, ground glass opacities, and, in later stages, honeycombing may be seen.

–Associated hilar and mediastinal adenopathy are characteristic of stage I

and II sarcoidosis.

No specific test is the gold standard, which emphasizes the importance of a multidisciplinary consensus for diagnosis with clinical, radiologic, and pathologic findings.

TREATMENT

Evidence does not support the routine use of any specific therapy for ILD in general, especially IPF (2,3).

No survival benefit of home oxygen use in ILD

Corticosteroids have a role in some ILD subtypes.

Current evidence does not clearly support routine use of noncorticosteroid anti-inflammatory agents for IPF, including cyclosporine, colchicine, cyclophosphamide, cytokines, sildenafil, dual endothelin receptor antagonists (bosentan, macitentan), etanercept, methotrexate, or interferon.

Clinical trials have indicated that anticoagulation (warfarin), ambrisentan,

mebooksfree.com

imatinib, and the combination of prednisone, azathioprine, and N- acetylcysteine are ineffective, potentially harmful, and therefore not recommended in the treatment of IPF (3)[A].

Recombinant human thrombomodulin improved 3-month survival in the setting of acute exacerbation of IPF in a small historical control study

GENERALMEASURES

Avoid/minimize offending environmental/occupational exposures/medications.

Smoking cessation

Supplemental oxygen, if indicated

MEDICATION

First Line

Corticosteroids are most effective for certain ILDs, especially exacerbations of sarcoidosis, NSIP, COP, and hypersensitivity pneumonitis. However, response rates have been variable across and within subtypes. The optimal dose and duration of therapy are unknown.

Common starting dose of prednisone is 0.5 to 1.0 mg/kg/day for 4 to 12 weeks with potential up-titration based on patient response.

Second Line

Two antifibrotic agents approved for IPF exhibited modest slowing of FVC decline over 52 weeks compared to placebo. Both decreased all-cause mortality rates. It is not clear if FVC is the most conclusive meaningful efficacy variable for IPF.

–Pirfenidone (Esbriet) decreased the rate of decline in FVC compared to placebo. Secondary trial findings include a significant improvement in progression-free survival, and pooled analysis reveals a significant reduction in all-cause death and death from IPF. The most common adverse effects are GI related (nausea, vomiting, anorexia, weight loss, GERD and dyspepsia), rash, insomnia, dizziness, fatigue, and aminotransferase elevation. Most AEs are mild to moderate in nature and do not result in pirfenidone discontinuation. Pirfenidone is not recommended for patients with severe liver impairment or ESRD (4)[A].

–Pirfenidone is titrated over 2 weeks to 801 mg orally 3 times daily with food.

–Nintedanib (Ofev), reduced the annual rate of decline in FVC, and fewer

mebooksfree.com

acute exacerbations occurred compared to placebo. The most common adverse effects are GI upset (nausea, vomiting, diarrhea, abdominal pain), anorexia, aminotransferase elevation, and hypertension. It is not recommended in moderate to severe liver impairment and can cause birth defects (5)[A].

– Nintedanib is given at 150 mg orally twice daily with food. The addition of tacrolimus to corticosteroids (with cyclosporine,

cyclophosphamide, or no additional therapy) demonstrated improved eventfree survival in patients with ILD complicated with polymyositis or dermatomyositis.

Several second-line agents have been used in Wegener granulomatosis:

–Cyclophosphamide is commonly used in treatment of Wegener granulomatosis. It is given 1.5 to 2.0 mg/kg/day PO for 3 to 6 months.

–Methotrexate has been used in treatment of mild Wegener granulomatosis in combination with corticosteroids; a studied dosing regimen consisted of an initial dose of 0.3 mg/kg (max dose of 15 mg) once weekly, with 2.5 mg titration each week (max dose of 25 mg/week)

–Other second-line agents that have been studied include mycophenolate, mofetil, and rituximab.

SURGERY/OTHER PROCEDURES

Singleor double-lung transplantation may be a treatment of last resort. Lung transplant among selected IPF patients has demonstrated median survival of 4.5 years (6)[A]. Some ILDs associated with systemic disease may recur in the recipient lung.

Alveolar type II cell intratracheal transplantation has been shown to be welltolerated and potentially beneficial in patients with moderate to progressive IPF at 12 months (7).

Clinical trials to assess the safety and efficacy of allogeneic human mesenchymal stem cell infusion in patients with mild to moderate IPF are ongoing (8).

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Follow-up testing should include PFTs, cardiopulmonary stress test, pulse oximetry, and CXR.

mebooksfree.com

PATIENTEDUCATION

National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/

PROGNOSIS

IPF confers the worst prognosis (median survival of 2.5 to 3 years). Aclinical prediction model to estimate the risk of death from ILD has been described (ILD-GAPmodel). Other subtypes, including hypersensitivity pneumonitis, NSIP, and COP, have a good prognosis.

COMPLICATIONS

Cor pulmonale

Pneumothorax

Progressive respiratory failure

REFERENCES

1.Kurland G, Deterding RR, Hagood JS, et al; for American Thoracic Society Committee on Childhood Interstitial Lung Disease (chILD) and the chILD Research Network. An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy. Am J Respir Crit Care Med. 2013;188(3):376–394.

2.Raghu G, Collard HR, Egan JJ, et al; for ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.

3.Raghu G, Rochwerg B, Zhang Y, et al; for American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, Latin American Thoracic Association. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3–e19.

4.King TE Jr, Bradford WZ, Castro-Bernardini S, et al; for ASCEND Study Group. Aphase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–2092.

5.Richeldi L, du Bois RM, Raghu G, et al; for INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22): 2071–2082.

6.Kistler KD, Nalysnyk L, Rotella P, et al. Lung transplantation in idiopathic pulmonary fibrosis: a systematic review of the literature. BMC Pulm Med.

mebooksfree.com

2014;14:139.

7.Serrano-Mollar A, Gay-Jordi G, Guillamat-Prats R, et al; for Pneumocyte Study Group. Safety and tolerability of alveolar type II cell transplantation in idiopathic pulmonary fibrosis. Chest. 2016;150(3):533–543.

8.Glassberg MK, Minkiewicz J, Toonkel RL, et al. Allogeneic human mesenchymal stem cells in patients with idiopathic pulmonary fibrosis via intravenous delivery (AETHER): a phase I safety clinical trial. Chest. 2017;151(5):971–981.

CODES

ICD10

J84.9 Interstitial pulmonary disease, unspecified

J84.10 Pulmonary fibrosis, unspecified

J84.111 Idiopathic interstitial pneumonia, not otherwise specified

CLINICALPEARLS

ILD differs from chronic obstructive pulmonary disease (COPD); anatomically, ILD involves the lung parenchyma (i.e., alveoli), and COPD involves both airways and alveoli.

In some cases, avoiding or minimizing offending environmental/occupational exposures, medications, and smoking may alter disease severity.

mebooksfree.com

DIVERTICULAR DISEASE

Jin Sol Oh, MD Brian P. Bateson, DO Steven B.

Holsten Jr., MD, FACS

BASICS

DESCRIPTION

Diverticulum (single) or diverticula (multiple) are outpouchings in the colonic wall. Diverticular disease is a spectrum of diseases:

Asymptomatic diverticulosis: common incidental finding on routine colonoscopy

Symptomatic diverticulosis: also known as symptomatic uncomplicated diverticular disease (SUDD); recurrent abdominal pain attributed to diverticulosis without colitis or diverticulitis (1)

Acute diverticulitis: inflammation and/or infection

–Uncomplicated diverticulitis: left lower quadrant (LLQ) pain, tenderness, leukocytosis, but no peritoneal signs or systemic toxicity

–Complicated diverticulitis: secondary abscess formation, bowel obstruction

or perforation, peritonitis, fistula, or stricture Diverticular bleeding

–Accounts for >40% of lower GI bleeds and 30% of cases of hematochezia in general

–Bleeding more common with right-sided diverticula

System affected: entire GI tract except the rectum

EPIDEMIOLOGY

Incidence

Diverticular disease accounts for ~300,000 hospitalizations per year in the United States.

Diverticulitis occurs in 1–2% of the general population and in 4% of patients with diverticulosis over the course of their lifetime (1).

Diverticular bleeding occurs in 3–5% of patients with diverticulosis.

Prevalence

Prevalence of diverticulosis and the number of diverticula increase with age

mebooksfree.com

–Diverticulosis occurs in 60% of the population >age 60 years and 70% by the age of 80 years.

–Increased from 62 to 75/100,000 persons from 1998 to 2005; large increase

in incidence for patients <45 years of age, due to changes in diet

Male = female overall; more common in men <65 years of age and more common in women >65 years

ETIOLOGYAND PATHOPHYSIOLOGY

Adiverticulum forms where intestinal blood flow (vasa recta) penetrates the colonic mucosa. This results in decreased resistance to intraluminal pressure.

Age-related degeneration of mucosal wall, increased intraluminal pressure from dense, fiber-depleted stools, and abnormal colonic motility contribute to diverticulosis.

Most right-sided diverticula are true diverticula (all layers of the colonic wall).

Most left-sided diverticula are pseudodiverticula (outpouchings of the mucosa and submucosa only).

Diverticulitis occurs when local inflammation and infection contribute to tissue necrosis with risk for mucosal microor macroperforation.

Diverticulitis: Microscopy reveals inflammation with lymphocytic infiltrate, ulceration, mucin depletion, necrosis, Paneth cell metaplasia, and cryptitis.

Alterations in intestinal microbiota contribute to chronic inflammation (1,2).

Thinning of the vasa recta over the neck of the diverticula increases susceptibility to bleeding.

Diverticular disease and irritable bowel syndrome (IBS) may represent the same disease continuum.

Genetics

No known genetic pattern

Asian and African populations have lower overall prevalence but develop diverticular disease with adoption of a Western lifestyle.

RISK FACTORS

Age >40 years

Low-fiber diet

Sedentary lifestyle, obesity

Previous diverticulitis. Risk rises with the number of diverticula.

Smoking increases the risk of perforation (1).

Diverticular bleeding: increased risk with NSAIDs, steroids, and opiate

mebooksfree.com

analgesics. Calcium channel blockers and statins appear to be protective against diverticular bleeding.

GENERALPREVENTION

High-fiber diet or nonabsorbable fiber (psyllium)

Vigorous physical activity

COMMONLYASSOCIATED CONDITIONS

Colon cancer, connective tissue diseases, and inflammatory bowel disease

DIAGNOSIS

HISTORY

Diverticulosis

–80–85% of patients are asymptomatic. Of the 15–20% with symptoms, 1– 2% will need hospitalization, and 0.5% will need surgery.

–Abdominal pain is most common symptom: dull, colicky, primarily LLQ. Pain can be exacerbated by eating and by passing bowel movement or flatus.

–Diarrhea or constipation

Acute diverticulitis: uncomplicated (85%) and complicated (15%)

–Abdominal pain: acute onset, typically in LLQ

–Fever and/or chills

–Anorexia, nausea (20–62%), or vomiting

–Constipation (50%) or diarrhea (25–35%)

–Dysuria and urinary frequency suggest bladder or ureteral irritation.

–Pneumaturia and fecaluria with colovesical fistula

Diverticular bleeding

–Melena, hematochezia

–Painless rectal bleeding

Immunocompromised patients may not present with fever or leukocytosis but are at higher risk for perforation and abscess formation (2).

PHYSICALEXAM

Diverticulosis

–Usually normal

–May have intermittent distension or tympany

mebooksfree.com

– May have heme + stools

Acute diverticulitis

–Abdominal tenderness (usually LLQ)

–Abdominal distension and tympany

–Rebound tenderness, involuntary guarding, or rigidity suggests perforation and/or peritonitis.

–Palpable mass in LLQ (20%)

–Bowel sounds hypoactive (could be high-pitched and intermittent if obstruction is present)

–Rectal exam may reveal tenderness or mass.

–Colovaginal, colovesical, and perirectal fistulae are rarely the initial presentation.

DIFFERENTIALDIAGNOSIS

Urinary tract infection, nephrolithiasis, IBS, lactose intolerance, carcinoma, inflammatory bowel disease, fecal impaction, bowel obstruction, angiodysplasia, ischemic colitis, acute appendicitis, ectopic pregnancy

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Diverticulosis: no labs or imaging needed Acute diverticulitis

–WBC is normal in up to 45% of cases. As diverticulitis worsens, WBC elevated with left shift.

–Hemoglobin normal (unless bleeding)

–ESR elevated

–Urinalysis may show microscopic pyuria or hematuria.

–Urine culture: usually normal; persistent infection suspicious for colovesical fistula

–Blood cultures positive in systemic cases

–Plain films of the abdomen (acute abdominal series—supine and upright) to assess for free air under the diaphragm (bowel perforation) and signs of bowel obstruction (dilated loops of bowel)

–CT scan with IV, oral, and/or rectal contrast (sensitivity: 98%, specificity: 99%) to stage disease and determine treatment plan (3)[A]

–Ultrasound and MRI (sensitivity: 94%, specificity: 92%) are useful alternatives.

–Barium enema is not recommended due to risk of peritoneal extravasation.

mebooksfree.com

Diverticular bleeding

–Decreased hemoglobin with bleeding

–Obtain coagulation panel for coagulopathy.

Diagnostic Procedures/Other

Diverticular bleeding

–Endoscopy to evaluate GI bleeding (4)

–NG lavage to exclude upper GI bleeding (4)

–Angiography if bleeding obscures endoscopy or when endoscopy cannot visualize a source (4)

–99mTc-pertechnetate–labeled RBC scan (more sensitive) with follow-up angiography to localize bleeding (not studied in a comparison trial) (4)

TREATMENT

GENERALMEASURES

Diverticulosis: outpatient therapy with fiber supplementation and/or bulking agents (psyllium) (>30 g/day) (3)[A]

Uncomplicated diverticulitis: outpatient therapy with or without oral antibiotics. 1–2% of subjects require hospitalization for toxicity, septicemia, peritonitis, or failure of symptoms to resolve. Up to 30% of patients may require surgery at first episode of diverticulitis.

Complicated diverticulitis: hospitalization, bowel rest, and IV antibiotics. Hinchey classification (severity):

–Stage I: diverticulitis + confined paracolic abscess

–Stage II: diverticulitis + distant abscess

–Stage III: diverticulitis + purulent peritonitis

–Stage IV: diverticulitis + fecal peritonitis

Symptomatic improvement is expected within 2 to 3 days. Antibiotics should be continued for 7 to 10 days.

Diverticular bleeding: 80% of cases resolve spontaneously (4).

MEDICATION

First Line

Symptomatic diverticulosis: cyclical rifaximin 400 mg PO BID for 7 days every month or continuous mesalamine 800 mg PO BID (3)[C]

Acute diverticulitis

mebooksfree.com