Background (Eur Respir J 2005;26:720)
Pulmonary function testing refers to a suite of measurements which are used to assess air movement, volume, and diffusion capacity of the lungs; these tests are used to diagnose, assess severity of, and follow course of major pulmonary diseases
Spirometry: “fundamental” PFT—measures volume and flow of air with inspiration & expiration; pt takes deep breath and exhales as forcefully as possible into the spirometry tube; this test provides:
Forced vital capacity (FVC): Volume of air a person can exhale for the duration of the test during max effort: Pt inhales as deeply as possible, then exhales as long and forcefully as possible, should last ≥6 s; ↓ in restrictive disease Forced expiratory volume (FEV1): volume of air expelled in the 1st s at max effort FEV1/FVC: % of
FVC expired in 1st second; ↓ in obstructive disease Bronchodilator response: Test may be repeated after administration of SABA; allows to assess for reversibility of obstructive component (e.g., distinguishes asthma from COPD); fully reversible defined as FEV1 ↑ by 200 mL & 12%
Plethysmography: Used to measure lung volumes; pt placed in large airtight box (w/ clear walls) w/ breathing tube and asked to inspire with mouth on a shutter valve; subsequent change in box pressure + Boyle’s law (P1V1 = P2V2) used to calculate lung volumes (alt: nitrogen or
helium gas washout); key measurements include: provides →
Total lung capacity (TLC): Total amt of air lungs can hold, ↓ in restrictive disease Residual volume (RV): Amt of air left in lungs after complete exhalation
DLCO: Diffusing capacity of lung (ability for gas exchange), measured
using carbon monoxide (counsel pts to avoid cigarettes, SABA on day of test as possible; if on supplemental O2, avoid 15 min prior to test if possible)
Spirometry may be done in office setting, whereas lung volumes and
DLCO are typically measured in dedicated laboratory
If performing spirometry in primary care office: Examine pt effort and flow loops for validity and reversibility; poor validity if: Forced expiration ≤6 s (will mimic restriction), distortion of flow loops due to cough on expiration (will mimic obstruction), delay of peak flow maneuver or poor peak flow effort (will mimic obstruction), FVC maneuver does not end in a plateau
Interpretation (AFP 2014;89:259)
Obstructive pattern characterized by low FEV1/FVC; restrictive pattern characterized by ↓TLC; mixed/overlap syndromes may exist (e.g., obesity + COPD); consider referral if restrictive lung disease or interpretation unclear
Courtesy of A. Luks
Courtesy of A. Luks
| Typical PFT Results, by Disease | ||||
| Disease | FEV1 | FVC | FEV1/FVC | Notes |
| Asthma | Nl/↓ | Nl | Nl/↓ | May be nl in mild– mod disease; obstructive deficit reversible w/bronchodilator |
| COPD |
↓ |
Nl |
↓ |
See COPD; deficit not reversible w/ bronchodilator |
| Restrictive lung disease (due to lungs, e.g., ILD) | nl |
↓ |
nl | DLCO decreased; order lung volumes to confirm |
| Restrictive lung disease (external |
↓ |
↓ |
nl | DLCO normal; order lung volumes |
Background (NAMCS 2010, cdc.gov/nchs/ahcd; NHLBI 2007, nhlbi.nih.gov/guidelines/asthma)
Definition: Chronic inflammatory disease of airways → episodes of airflow limitation → classic triad of sx (wheezing, cough, & dyspnea); over time can → airway remodeling (fibrosis, smooth muscle hypertrophy) → fixed obstructive component
“Asthma-plus” syndromes: Atopy (asthma + allergic rhinitis + atopic dermatitis), Samter’s triad (asthma + ASA sensitivity + nasal polyps), Allergic Bronchopulmonary Aspergillosis (ABPA) (asthma + bronchiectasis+ allergic reaction to aspergillus), Churg–Strauss (asthma + eosinophilia + granulomatous vasculitis) (Lancet 2002;360:1313) Pathophysiology: Genetic (predisposition for IgE-mediated/Th2
response) & environmental factors (pollution, tobacco, allergens) → altered immune response → airway hyperresponsiveness, bronchoconstriction, ↑ edema/mucus → airflow obstruction Epidemiology: Affects ~8% of US adults, ♀ > ♂; African-American > Caucasian > Hispanic; onset in majority of pts occurs by age 40 y Risk factors: Atopy, smoking, obesity, occupational exposure (adult onset), dust mite exposure (childhood onset); rural upbringing protective (thought to be 2/2 ↑ diversity of microbial exposure) (NEJM 2013;369:549)
Diagnosis
Hx/PE and spirometry used to diagnose and assess comorbidities, triggers and severity
History: Classic sx: Intermittent episodes of dyspnea, chest tightness, wheezing, cough, frequently w/ identifiable triggers (below), often early- AM or nighttime coughing
PMHx: Atopy (atopic dermatitis, allergic rhinitis), seasonal allergies, rhinitis/sinusitis, GERD, CHF, OSA, obesity, depression/anxiety,
vocal cord dysfunction Meds: ASA/NSAIDs (use or hx sensitivity), βB, ACEI
FHx: Asthma, atopy, other pulm diseases
Social hx: Tobacco exposure, occupational & home exposures, incl pets
Exam: Often unremarkable exam if not in acute exacerbation; HEENT (nasal polyps, allergic “shiners” or rhinitis), skin (atopic dermatitis), full chest & pulm exam
Spirometry: Recommended in all pts in whom asthma is considered; documents obstruction (FEV1/FVC <70%) & its potential reversibility (FEV1 ↑ by 200 mL & 12% w/ bronchodilator); however, spirometry can be nl in mild disease btw episodes; pts may fail to show reversibility if asthma very poorly controlled; see “Pulmonary Function Tests”
Labs: Not routinely indicated; if severe asthma, consider serum IgE,
CBC w/ diff (↑eos), skin testing/RAST (typically by allergy/immunology specialist)
Other: Methacholine challenge: Induced bronchospasm demonstrates airway hyperresponsiveness; occasionally used if PFTs nl and/or cough-variant asthma suspected; Se >90% (ARJCCM 2000;161:309), trial of empiric tx typically preferred; Sputum: >3% eosinophils has Se 86%, Curschmann spirals (mucous casts), Charcot–Leyden crystals (eosinophil lysophospholipase); CXR/advanced imaging if indicated by Ddx
Differential diagnosis: COPD, PE, CHF, bronchiectasis, hypersensitivity pneumonitis, eosinophilic lung disease, tracheobronchomalacia, mechanical airway obstruction, (tumor), ABPA, med-induced cough (ACEI), vocal cord dysfunction (see “Hoarseness”)
Evaluation (NEJM 2001;344:350)
General approach: Patients w/ asthma should be assessed for symptom control, medication/tx adherence, and trigger exposure to determine management plan
Asthma history: age of onset, exacerbations (PO steroids, ED, inpatient, intubation); recent poor control/hx intubation assoc w/ ↑ asthma mortality (Chest 2003;124:1880), peak flow
| Allergens | Persistent: Dust mites, cockroaches, pets, Seasonal (some regional
variability): trees (spring), grass (summer), weed pollen (fall) |
| Occupational | Smoke, irritants, mold |
| Meds/toxins | Tobacco smoke exposure, outdoor air pollution, perfumes, ASA, NSAIDs, nonselective βB (though some controversy) |
| Infections | Viral upper respiratory infections |
| Other | Stress, cold air, strenuous physical activity, food additives (sulfites), hard laughing/crying |
Current control: For pts already on treatment, review current inhaler adherence and technique, as well as current symptoms, can use Asthma Control Test (qualitymetric.com/act; score >20 indicates control)
Exam: often unremarkable; wheezing on routine exam suggests poor control/exacerbation
Peak flow: Used to assess control (comparing current test against personal best), but improvement by 20% w/ bronchodilator can be used to support dx; n.b. reduced peak flow ≠ airway obstruction
Treatment (NEJM 2009;360:1002)
Nonpharmacologic treatment: Indicated for all pts, multifaceted approach beneficial
Allergen avoidance: Dust mites: Use bedding encasements, wash sheets weekly in hot water, avoid down, HEPA vacuum or air filter, no carpet in bedroom; pets: ↓ pet exposure (pet-free home or at least keep out of bedroom); eliminate mold/moist conditions when possible (↓ indoor humidity); Cockroach: Extermination, no exposed food or garbage; Pollens (indoors w/ windows closed during peak season); consultation with allergy specialist may be helpful Irritant avoidance: Avoid outdoor exercise during periods of ↓ air quality (airnow.gov/ offers US air quality forecasts), avoid exposure to wood stoves, tobacco smoke Smoking: Smoking & 2nd-hand smoke may ↓ response to asthma medication, ↓ lung function, & trigger exacerbations; counsel all pts & family members to quit (see “Tobacco Use”) & ask housemates to smoke outside (AJRCCM 2007;175:783) Immunizations: Influenza & pneumococcal vaccines recommended; see “Immunizations”
Patient education: Key to trigger avoidance, effective inhaler use; see “Tip Sheets” at www.nhlbi.nih.gov/health/public/lung/asthma/asthma_tipsheets.pdf
Asthma action plan: Pts & providers should establish an asthma action plan, using sx or peak flow: sample at www.nhlbi.nih.gov/health/public/lung/asthma/asthma_actplan.pdf
Pharmacologic Treatment
General Approach: Initial tx dictated by severity; subsequent tx dictated by degree of control; all pts should have “rescue” inhaler Rx; All other Rx’s are “controller”: effective in preventing/reducing sx over long-term, not useful in acute management of sx
Initiating treatment: For pts not currently treated, determining which “step” to start on determined by severity assessment (below); pt category determined by most severe sx
Continuing treatment: For pts currently treated, assess control (see above) and then step up, down, or maintain as indicated; pt & provider judgment of tx efficacy should be guide; if asthma not well controlled, assess inhaler adherence & technique before modifying tx
| Classification of Asthma Severity | ||||
|
Intermittent |
Persistent | |||
| Mild | Mod | Severe | ||
| Sx frequency | ≤2 d/wk | >2 d/wk | Daily | Daily |
| Nighttime awakenings | ≤2×/mo | 3–4×/mo | >1/wk | Nightly |
| SABA use for sx control | ≤2 d/wk | >2 d/wk | Daily | Several times/d |
| Interference w/ nl activity | None | Minor | Some | Extreme |
| Spirometry (% predicted) | Nl btw
exacerbations |
Nl btw
exacerbations |
FEV1: 60–80%
pred; FEV1/FVC: ↓ |
FEV1: <60%
pred; FEV1/FVC: ↓ |
| Exacerbations | <1/y | ≥2/y | ≥2/y | ≥2/y |
| Initial Tx | Step 1 | Step 2 | Step 3 | Step 4 or 5 |
| Asthma Treatment Steps | ||||
| Step | Controller Medication | ||
| Step 1 | None indicated (should receive SABA PRN) | ||
| Step 2 | Low-dose ICS, consider allergen immunotherapy
Alt: Antileukotriene, theophylline, cromolyn |
||
| Step 3 | Low-dose ICS & LABA
Alt: Medium-dose ICS, low-dose ICS + (LTRA, theophylline, or zileuton); consider adjunct tiotropium, allergen immunotherapy |
||
| Step 4 | Med-dose ICS & LABA, specialist referral Alt: Med-dose ICS & (LTRA, theophylline, or zileuton); consider adjunct tiotropium, allergen immunotherapy | ||
| Steps 5, 6 | High-dose ICS + LABA ± oral corticosteroids, specialist referral, consider anti-IgE therapy or anti-IL5 therapy if appropriate phenotype | ||
| Features of Well-Controlled Asthma | |||
| No limitation of activities
No nocturnal sx/awakenings Validated survey indicating control (see above) |
PEF or FEV1 nl Reliever/rescue tx ≤2 d/wk Daytime sx ≤2 d/wk | ||
| Treatment Plan by Level of Control | |||
| Well-controlled: All control criteria met or n/a | <3 mo: maintain regimen; ≥3 mo: consider step-down reassess in 1-6 mo | ||
| Partially controlled: 1–2 of the listed criteria not met | Step-up 1 step Reassess in 2–6 wk | ||
| Poorly controlled: ≥3 of the listed criteria not met | Step-up 1–2 steps: Consider short course PO corticosteroids (40–60 mg QD × 3–10 d) Reassess in 2 wk | ||
When to Refer
Patients with “asthma-plus” syndromes; pts w/ mod–severe asthma or poorly controlled/frequent exacerbations despite escalation of Rx; dx uncertain, prior hospitalization for asthma → specialist (pulm or allergy/immunology)
Patients with prominent allergic component → allergyimmunology for allergy testing, consideration of allergen immunotherapy
ASTHMA MEDICATIONS
Inhalers: Multiple devices (below); pt education key, as many use
inhalers incorrectly (AJRCCM 1994;150:1256); inhaler how-to videos at cdc.gov/asthma/inhaler_video/default.htm
| Inhaled Medication Delivery Systems (nhlbi.nih.gov) | |
| Metered-dose inhaler (MDI) | Aerosolized Rx; must be “primed” (discarded sprays) before 1st use; requires coordination of actuation & breath Deep slow breath × 3–5 s, then hold × 10 s; repeat after 1 min if dose is “2 puffs” |
| Spacer | Used w/ MDI; turns aerosol into finer droplets for ↑ delivery to lungs; ineffective if pt exhales into spacer; requires separate Rx |
| Valved holding chamber (VHC) | Similar to spacer but prevents pt exhaling into device, may be more expensive; requires Rx |
| Dry powder inhaler (DPI) | Powdered Rx drawn into lungs w/ inhalation; can clump w/ ↑ humidity; use fast, deep breath & hold for 10 s |
| Nebulizer | Requires nebulizer machine to deliver Rx; no more effective at Rx delivery, but does not require pt effort/coordination |
“Quick-relief” or “rescue” inhaler: Should be prescribed for all pts; to be used PRN or as ppx prior to anticipated exposure (e.g., exercise)
Short-acting beta agonists (SABA, e.g., albuterol): Mainstay and should be prescribed for all pts; onset <5 min, peak 30–60 min, duration 4–6 h; S/e: Tremor, tachycardia, anxiety, palpitations Short-acting anticholinergics (e.g., ipratropium): less-effective alternative in pts w/ mild sx who do not tolerate SABA or as adjunct in pts w/ severe sx; not FDA-approved
Inhaled corticosteroids (ICS): controller Rx
Mechanism: ↓ airway inflammation & bronchial hyperresponsiveness
→ fewer asthma sx, ↑ lung function, ↑ QoL, ↓ exacerbations & ↓ mortality (JAMA 1997;277:887; NEJM 2000;343:332) S/e: Hoarseness, sore throat, oral candidiasis; can → systemic s/e in ↑ doses (e.g.,
>1000 μg beclomethasone/d) Dosing: Delivered by DPI or HFA (see above) and divided into low, medium, or high dose: determined by individual steroid’s potency, concentration (“dose/puff”), and number of inhalations (“puffs”) Example Rx: fluticasone offered at 3 strengths (44 mcg/inh, 110 mcg/inh, and 220 mcg/inh); low dose = 88–264 mcg/d, med dose = 264–440 mcg/d, high dose >440 mcg/d Best to pick one agent and step up/down; use conversion chart to switch agents Pt education:
rinse mouth after use, if delivery vehicle is MDI, use w/ spacer or VHC
Combination ICS + long-acting beta agonist (LABA): In asthma, LABA always used in combination w/ ICS 2/2 risk of ↑ asthma- related deaths (Chest 2006;129:15), though some believe risk may be overstated (NEJM 2016;375:850)
Benefits: Combination tx → sustained improvement in lung function, ↓ in sx, exacerbations, ICS dose (Cochrane Database Syst Rev 2010;4:CD005533) Dosing: In combination inhalers, LABA dose constant but ICS may come in different strengths; most inhalers are BID, although some newer agents (e.g., Breo, fluticasone- vilanterol) are QD; may have to Rx LABA and ICS as separate inhalers (to be used together) depending on insurance formulary Example Rx: Fluticasone/salmeterol 100 mcg/50 mcg inh BID, 200/50 mcg inh BID, or 500 mcg/50mcg inh BID
S/e: Usually mild; muscle cramps, ↑ HR
Leukotriene modifiers: Used as adjunct/alternative to ICS; also effective for AR, may be preferable to ICS in pts w/ mild sx and allergic component; also consider in obese, smokers, ASA hypersensitivity; additive benefit to ICS in exercise-induced bronchospasm (AJRCCM 2007;175:783; AJRCCM 2006;173:379; JACI 2012;130:535)
Dosing: PM dosing preferred for montelukast; onset is hours, peak few days Example Rx: Montelukast 10 mg PO QPM (leukotriene receptor antagonist); Zileuton XR 1200 mg BID (leukotriene formation inhibitor) S/e: Hepatitis (zileuton 2–4%, requires LFT monitoring), possible mood/behavior sx
Long-acting muscarinic antagonists (LAMA): Adjunct to ICS ± LABA; Not FDA-approved for asthma; adding tiotropium superior to doubling ICS dose re: ↑ asthma control days, PEF, & ↓ daily sx (NEJM 2010;363:1715); Can ↓ exacerbation freq when added to pts w/ sx despite LABA/ICS (NEJM 2012;367:1257) example Rx: tiotropium 18 mcg inh QD Other: Typically Rx’ed by specialist for pts w/ severe or refractory disease
Omalizumab: Anti-IgE; SC q2–4wk; >$10K/y; must have ↑ IgE & sensitization to perennial aeroallergen (e.g., dust mite, pet) S/e: Local reaction, anaphylaxis (rare) Mepolizumab: Anti-IL5; pts w/
poorly controlled asthma on high-dose ICS with ↑eos; found to
↓exacerbation rate, ED visits/hospitalizations (NEJM 2014; 371:1198)
Theophylline: Can be useful in refractory disease; narrow therapeutic window (can → arrhythmia, N/V, HA, sz) Mast-cell stabilizer: Cromolyn sodium, Nedocromil: Specific benefit for ASA-sensitive pts or exercise-induced asthma; few s/e (AJRCCM 2002;165:9; Ann Intern Med 2000;132:97)
EXACERBATIONS
Definition: Acute onset/worsening of asthma symptoms (AFP 2011;84:40) Presentation: hx: Cough, wheeze, chest tightness, some limitation of activity; Exam: ↑ work of breathing on exam, wheezing, tachypnea; Peak flow: <80% (<40% consistent w/ severe exacerbation)
Red flags: Severe SOB, failure for peak flow to improve after quick- acting rx used, sx not improving 24 h after step-up → severe exacerbation → ED
Management of mild–mod exacerbation: (Some limitation of activity, peak flow 50–80% personal best): SABA 2–6 puff (or neb) now then Q2–4h PRN; step-up to next level of care; low threshold for short- course oral corticosteroids (40–60 mg prednisone QD × 3–10 d), esp if sx fail to improve w/ initial rescue Rx
Background (NEJM 2010;362:1407; GOLD 2016 Report, goldcopd.org; NHAMCS 2010, cdc.gov)
Definition: COPD is a chronic, often progressive pulmonary disease characterized by airflow limitation and assoc w/ exposure to noxious particles, most commonly tobacco
Pathophysiology: Genetic predisposition + toxic inhalants → airway inflammation, mucus hypersecretion, parenchymal destruction (with emphysema) → persistent, sometimes progressive airflow limitation in
small airways (Lancet 2012;379:1341)
Etiology: Most cases assoc w/ smoking (cigarette, cigar, pipe); biomass fuels (wood, coal, or dung stoves) & occupational exposures (dusts, gases, fumes) also contributors; genetics (α1-antitrypsin deficiency accounts for 1–2% of cases)
Epidemiology: 6.3% of US adults report COPD dx; >50% of pts w/ mild–mod cases underdiagnosed (MMWR 2012;61:938; Arch Intern Med 2000;160:1683); more common in pts aged 65–74 y, whites, ♀, hx asthma,
⊕ FHx; accounts for >5% of US outpt visits
Evaluation (NEJM 2010;362:1407, GOLD 2011)
General approach: Clinical diagnosis, confirmed w/ spirometry (need postbrochodilator testing); distinguished from asthma by smoking/exposure hx & incomplete bronchodilator reversibility (see “PFTs”) (though recent interest in asthma/COPD overlap syndrome,
NEJM 2015; 373:1241)
History: Cough, DOE or ↓ exercise tolerance, ↑ sputum production;
± wheezing, frequent chest infections; wt loss/anorexia in advanced disease; ↑ suspicion in current/former smokers
Meds/Toxins: Smoking hx: Calculate cumulative pack-years (packs/d
× number of years smoked); occupational exposure to biomass fuel (esp if foreign-born)/dusts/chemicals PMHx: Comorbidities— CAD, CHF, anxiety, depression, osteoporosis FHx; hx asthma or atopy, hx emphysema (especially in nonsmokers)
For patients with known COPD:
COPD hx: Exacerbation freq, prior hospitalizations, results of sputum cx Sx assessment: CAT (COPD Assessment Test) (catestonline.org); Clinical COPD questionnaire (http://ccq.nl/); mMRC (modified Medical Research Council) dyspnea scale. (Chest 2009;136:1473–1479) Staging: GOLD advocates for combined assessment using severity of obstruction or h/o disease activity (exacerbations/hospitalizations) and symptoms to determine staging (A–D); A = low risk, less sx, B = low risk, more sx, C = high risk, less sx, D = high risk, more sx; goldcopd.org
Exam: Can be nl in mild disease; varied presentation can include pursed-lip breathing,↑ AP diameter, hyperresonance, distant breath sounds, prolonged expiration, wheezing, cachexia (late stage); clubbing
not sign of COPD (think: liver disease, ILD, cancer)
Spirometry: Obtained at dx, may be used to track disease progression; COPD dx requires obstruction (FEV1/FVC <0.7) not fully reversible after bronchodilator
FEV1 used to classify severity: mild >80% predicted; mod 50–80%;
severe: <50%
Bronchodilator response: Often minimal; marked response → FEV1/FVC >0.7 suggests asthma (see “Asthma,” “PFTs”) Other studies, if obtained (not needed for all pts): Lung volumes can assess for hyperinflation, airtrapping, or restrictive deficit (see
“PFTs”); DLCO measurement can assess degree/impact of
emphysema (and can be disproportionately low in PH); Note: peak flow may underestimate obstruction in COPD
Chest imaging: Consider baseline CXR; CT chest not indicated unless particular symptoms indicate complication, new pulmonary process, or if characterization of emphysema required
α1-antitrypsin testing (serum): Consider in pts <45 y, non/minimal smokers, or ⊕ FHx
Other: Baseline ECG; ABG in severe disease/hypoxemia (to assess alveolar ventilation)
Differential diagnosis (and comorbidities): Asthma, bronchiectasis, bronchiolitis, ILD, CHF, lung CA
Nonpharmacologic Therapy (NEJM 2010;362:1407; GOLD 2016; Eur Respir J
2004;23:932)
Smoking cessation: ↓ FEV1 decline & ↓ all-cause mortality (JAMA 1994;272:1497; Ann Intern Med 2005;142:233); see “Tobacco Use”
Supplemental oxygen: Long term: If PaO2 <55 mmHg or SpO2 ≤88%;
or If PaO2 <59 mmHg or SpO2 ≤89% and cor pulmonale, RV failure, or HCT >55; for goal SpO2 90–92%; ↓ all-cause mortality by 20% (Ann Intern Med 1980;93:391; Lancet 1981;1:681); counsel re: home O2 safety (smoking is absolutely contraindicated, tubing can be fall risk); Nocturnal/exercise: If PaO2 <55 mmHg or SpO2 ≤88%; Air travel or altitude: If resting SpO2 <92%, eligible for in-flight O2 (see “Travel Medicine”)
Vaccines: Influenza, pneumococcal (see “Immunizations”)
Pulmonary rehabilitation (inpatient and outpatient): ↑ functional capacity & QoL (Cochrane Database Syst Rev 2015;2:CD003793); includes conditioning, breathing retraining, education, and psychological support
Goals of care: Discussion indicated for all pts w/ mod–severe disease; explore/document preferences including intubation, tracheostomy; see “Advance Care Planning”
Pharmacotherapy (NEJM 2010;362:1407; GOLD 2016; Eur Respir J 2008;31:416–468)
No Rx proven to alter the long-term decline in lung function; used to ↓ sx, ↓ exacerbation severity/freq, improve functioning
Short-acting bronchodilators: β2-agonist (SABA) (i.e., albuterol) & anticholinergic (SAMA); (i.e., ipratropium) improve symptoms, health status
Nebs vs. MDI: Generally equivalent; see “Inhaled medications” in
“Asthma”
LABA: ↑ FEV1, ↓ sx, 25% ↓ in exacerbations, ↓ hospitalizations (Eur Respir J 1997;10:1696; Cochrane 2013;10:CD01017)
LAMA: ↑ FEV1, ↓ exacerbations, compared w/ LABA, 11% ↓ freq &
severity of exacerbations (NEJM 2011;364:1093); preferred to LABA monotherapy; now many LAMAs, some QD, some BID; equivalent to tiotropium; choice often dictated by insurance
LAMA/LABA: Improve sx and FEV1 compared with monotx (AJRCCM 2015;192(9): 1068–1079); may ↓ exacerbation frequency when compared w/LABA + ICS (NEJM 2016;374:2222)
ICS: Only in addition to LABA or tiotropium (↓ exacerbations, improve health status); not recommended as monotherapy (NEJM 2007;356:775); s/e include thrush, dysphonia (rinse mouth after use, use spacer w/ MDI—requires Rx)
LABA + ICS + LAMA (“triple therapy”): When compared w/ LABA + ICS alone, may ↓ mortality, PO glucocorticoid use, & hospitalizations, but prospective RCT lacking (Chest 2012;141:81; Cochrane 2011;3:CD008532); note: withdrawal of ICS from triple therapy does not increased risk of exacerbation) NEJM 2014; 371:1285–1294
Other: Typically Rx’ed by specialists for pts w/severe disease Roflumilast (PDE5 inhibitor): used as adjunct, ↓ exacerbation
frequency (AJRCCM 2016;194(5):559–567) Theophylline: May have bronchodilator effect in some patients (Lancet 2009;374:695–703) but requires monitoring for toxicity; typically slow release formulations used
Azithromycin ppx: 250 mg QD → ↓ exacerbation frequency by 27%, unknown long-term effects; concern for abx resistance, ↑ QTc, ototoxicity (NEJM 2011;365:689; 2012;367:340)
| Initial Approach to Therapy of Stable Disease (GOLD 2016) Recommended escalation & de- escalation strategy depending on clinical course; start with preferred regimen, then “step- up/down” to alternative | |
| GOLD Category | Regimen |
| A (FEV 50–80% predicted or <1 exacerbation/y; mild sx [e.g., CAT score
<10]) |
PRN SABA or SAMA
Alt: LABA, LAMA, SABA & SAMA |
| B (FEV 50–80% pred or <1 exacerbations/y; sx not well-controlled [e.g., CAT ≥10]) | LABA or LAMA Alt: LAMA/LABA |
| C (FEV1 < 50% pred or ≥2 exacerbations/y or
≥1 hosp; mild sx) |
LAMA or ICS/LABA Alt: LAMA/LABA |
| D (FEV1 <50% pred or ≥2 exacerbations/y or
≥1 hosp; sx not well-controlled) |
LAMA/LABA
Alt: ICS & LABA & LAMA, then consider PDE5 inhibitor, macrolide |
When to refer: Dx uncertain, severe/refractory disease, onset <40 y, consideration of add’l agents, frequent exacerbations/hospitalizations, transplant eval (5-y median survival) or lung volume reduction surgery (may ↓ mortality & ↓ sx) (Eur Respir J 2004;23:932; J Heart Lung Transplant 2006;25:75; NEJM 2003;348:2059)
ACUTE EXACERBATION
Definition: Change in SOB, cough, and/or sputum production beyond baseline variation
Etiology: 50–70% infectious; of these, ~50% viral, 50% bacterial (H. influenzae > S. pneumoniae, M. catarrhalis >P. aeruginosa esp in advanced disease > atypicals) though hard to distinguish colonizer vs.
pathogen; noninfectious environmental insults (smoke, air pollution) also precipitants (NEJM 2008;359:2355; Thorax 2006;61:250)
Diagnostics: Obtain CXR; consider sputum culture, ECG Differential diagnosis: CHF, PNA, PE may be more common causes of death in COPD exacerbation than resp failure (Chest 2009;136:376) When to refer: Failure of outpt tx, uncertain dx, impaired ADL’s, worsening gas exchange or SOB, AMS, poor home care → ED/admit
(Eur Respir J 2004;23:932)
Management (NEJM 2010;362:1407; GOLD 2016; Eur Respir J 2004;23:932)
| Pharmacologic Management | |
| Medication | Comment |
| Oxygen | Target SpO2 ≥88–92%; concern about ↑ PaCO2 risk often overstated |
| Bronchodilators | SABA + SAMA; nebs vs. MDI equivalent (Arch Intern Med 1997;157:1736.) Consider “stepping up” baseline regimen. |
| Glucocorticoids | ↓ recovery time, ↓ risk of early relapse, ↑ FEV1 & PaO2
Recommend prednisone 40 mg PO QD x 5 d; no difference in time to next exacerbation between 5-d vs. 2-wk course (JAMA 2013;309:2223) However, some pts may have h/o requiring higher doses or taper Consider PCP ppx if prolonged steroid course (see “PCP”) |
| Antibiotics | Outpt data lacking but likely ↓ tx failure, possibly ↓ mortality; consider if ↑ sputum production/purulence (Chest 2000;117:1638; Thorax 2007;62:29) Consider resistance patterns, ± pseudomonal coverage in adv disease In general, if used, low risk: macrolide, doxycycline, cefpodoxime; high risk (older, lower FEV1, high exacerbation freq, comorbidities): augmentin or FQ; h/o pseudomonal PNA: FQ |
Background (AJRCCM 2013;188:733)
Definition: Heterogeneous group of diseases, all characterized by replacement of normal lung parenchyma w/ varying degrees of inflammation and fibrosis; described by both clinical and pathologic diagnoses
Idiopathic pulmonary fibrosis (IPF): Most common form of ILD, usually presents in 6th–7th decades, ♂ > ♀; risk factors include smoking, ⊕
FHx, GERD (AJRCCM 2011; 183:788); pathologic correlate is usual interstitial pneumonitis (UIP)
Incidental lung abnormalities (ILA): Findings of fibrosis on imaging (CXR, CT chest, lung cuts of CT abdomen; clinical significance of findings w/o symptoms not yet clear) (AJRCCM 2012;185:1147) Epidemiology & risk factors: All very rare; most data for IPF, w/reported prevalence 7–16 cases/100,000 in US (AJRCCM 2006;174:810); risk factors vary by ILD
Clinical classification: Idiopathic (idiopathic interstitial pneumonias) or secondary (related to systemic disease): rheumatologic/connective tissue disorders (RA, SSc, MCTD, dermatomyositis), vasculitis, sarcoid, amyloid, IBD, malignancy, meds (chemotherapy, antirheumatologic agents, amiodarone), exposures (asbestos, silicosis, coal)
Pathologic classification: Many histopathologic patterns (UIP, NSIP, BOOP/OP, RBILD, DIP, LIP, DAD, EP, PAP, DAH)
Pathologic dx does not always = clinical dx (IPF = clinical dx, UIP = Pathologic dx; NSIP = Pathologic and clinical dx); some clinical ILD dx assoc w/ multiple histopathologic patterns (e.g., hypersensitivity pneumonia can be assoc w/ UIP, BOOP, or NSIP patterns on pathology) (AJRCCM 2013;188:733)
Presentation: Typically presents w/ DOE & dry cough; may also be incidental finding on imaging (see ILA, above)
Prognosis: Varies by form of ILD; IPF has worst prognosis, medial survival 2–3 y (AJRCCM 2011;183(4):431; Ann Intern Med 2012;156:684)
Evaluation (AJRCCM 2012;185:1147)
General approach: Early referral to pulmonary specialist recommended if suspect ILD
History: Detailed exposure hx (hobbies, occupations), medication hx, past medical history, s/sx of connective tissue disease, smoking hx, GERD
Exam: Vitals: SpO2 rest & exertion; Pulmonary: Bilateral fine inspiratory crackles (often referred to as “velcro” crackles; CV: Look for signs of PH, cor pulmonale; Ext: Look for clubbing (if longstanding); Skin/joint exam: Look for rashes, joint findings c/w CTD
Diagnosis: Based on clinical s/sx and imaging; pathology often but not
always required; PFTs may also support diagnosis
Imaging: High-resolution chest CT permits better visualization of pulm anatomy (secondary pulmonary lobule); expiratory phase assesses for “air trapping” present only in some ILDs (e.g., hypersensitivity pneumonia, bronchiolitis obliterans) and better characterizes airways disease
Imaging pattern may help support specific ILD diagnoses:
UIP (IPF): Peripheral reticular changes, honeycombing, traction bronchiectasis, +/– peripheral, subpleural, basilar-predominant GGO
NSIP: Characterized by GGO, though fibrotic NSIP can be difficult to distinguish from UIP
PFTs: Demonstrate restriction and impairment in gas exchange (nl FEV1/FVC ratio, ↓ FEV1, FVC, TLC, DLCO)
Labs: No routine labs; consider ANA, Anti-Ro, La, Jo-1, Scl70, ANCA, HSP, CPK, aldolase; Note: Sometimes ILD can precede systemic sx of CTD
Bx: Often, tissue dx required (with exception of UIP/IPF) Management: Treatment depends on ILD; newer options for IPF that prevent ↓ in FVC include pirfenidone (antifibrotic) and nintenanib (TKI) (NEJM 2014;370:2083; NEJM 2014;370:2071); for ILD secondary to
rheumatologic/connective tissue disorders, typically comanaged by pulmonary & rheumatology; PCPs should ensure pts current on immunizations, have oxygen Rx if appropriate, & support transplant candidacy if appropriate
Background (Lancet 2002;360:237)
Definitions: Sleep apnea: Disorder in which pts experience apneas (cessation of breathing) or hypopneas (shallow breathing) often → daytime hypersomnolence
Obstructive: Due to upper airway collapse/closure; Central: Due to ↓ respiratory drive; Mixed: Central pause → resumption of resp effort against relaxed/closed upper airway
Epidemiology: 2–14% of the general population, ♂ > ♀ (JAMA
2013;310:731)
Risk factors: Obstructive: Obesity, ♂ sex, age >50, postmenopausal, African-American descent, ⊕ FHx, EtOH use (Arch Intern Med 2002;162:893); Central: Assoc w/ Cheyne–Stokes breathing (assoc w/ CHF, prior stroke), opioid use
Pathophysiology: Sleep-induced relaxation of pharyngeal dilator muscles → repetitive pharyngeal collapse during sleep → apnea (≥10
- s) or hypopnea (30% ↓ airflow × ≥10 s) → recurrent arousals & desaturations
Complications: CV: ↑ risk HTN (NEJM 2000;342:1378), CAD (Eur Respir J
2006;28:596), stroke (NEJM 2005;353:2034), & death (Lancet 2005;354:1046);
Neurocognitive: ↓ cognitive performance, ↓ QoL, ↑ MVC, & work accidents (NEJM 1999;340:847)
Evaluation (JAMA 2013;310:731)
General approach: Suspicion based on hx/exam, confirmed w/ sleep study
History: Witnessed apneas/gasping (LR 3.3); snoring common but presence not useful for making diagnosis (LR 1.1); Absence of snoring makes OSA less likely (LR 0.12–0.45)
Daytime sx: Daytime hypersomnolence (most common sx in OSA, can use validated survey to track, e.g., Epworth Sleepiness Scale), cognitive dulling, morning HA PMHx: Poorly controlled HTN, CHF, CVA, DM, unexplained pHTN, polycythemia, ↑ PaCO2,
history of multiple motor vehicle crash Meds/Toxins: Respiratory depressants (opiates, sleep aids, EtOH)
Exam: Vitals: BP, BMI, SaO2; HEENT; septal deviation, turbinate hypertrophy, nasal polyps or nasal valve collapse, enlarged tonsils or uvula, macroglossia,↑ Mallampati score (obscured view of soft palate/uvula), ↑ neck circumference, micro/retrognathia; CV (cor
pulmonale, LVH)
Screening: Consider STOP-Bang score; 8 yes/no questions with high Se & high NPV for OSA; (loud Snoring, Tired/sleepy during the day, Observed apneas, high blood Pressure or HTN tx; BMI >35, Age >40, Neck circumference >40 cm/16 in, ♂ gender);
Scoring: 1 point for each criteria met; High risk: total score ≥5 or STOP score ≥2 and any of the following: BMI >35, male gender, or
large neck (Chest 2016;149:631)
Sleep study: Either lab-based polysomnography (PSG) or in select pts w/ high pretest probability, a home-based study; can be used in diagnosis and/or for titration of optimal CPAP Rx; records sleep stages using EEG, EMG, & eye movements; evaluates for respiratory events (≥10 s)
Apnea–hypopnea index (AHI): Sum of apneic & hypopneic episodes/h of sleep Dx: OSA diagnosed when AHI shows at least 5 events/h (mild = AHI 5–15, mod = AHI 16–30, severe = AHI >30)
Differential diagnosis: 1° snoring, hypothyroidism, med effects/sedatives
Management (J Clin Sleep Med 2009;5:263)
Behavioral: ↓ Wt; avoid EtOH/sedatives, positional Rx to avoid supine sleep, external nasal dilators (e.g., nasal adhesive strips), dental/oral appliance for patients with mild to moderate OSA who are intolerant of CPAP
Positive pressure ventilation: CPAP or BiPAP
CPAP: Generally 1st-line for OSA; ⊕ pressure “stents” upper airway open & prevents collapse; has been shown to ↓ BP & improve metabolic syndrome (NEJM 2011;365:2277), ↓ sleepiness/↑ performance (AJRCCM 2001;164:608) ↓ fatal & nonfatal CV events (Lancet 2005;354:1046) & ↑ EF in pts w/ CHF (NEJM 2003;348:1233) BiPAP:
Can try in pt intolerant of continuous ⊕ pressure, although more
expensive & not shown to ↑ adherence; used in patients who require high pressure; 1st-line for central sleep apnea, may be helpful if concomitant hypoventilation (e.g., COPD or obesity hypoventilation) APAP: Varies pressure based on flow, can try in pt intolerant of continuous ⊕ pressure
Surgery: Consider referral in refractory disease or severe disease w/CPAP intolerance; nasal surgery can improve nasal CPAP adherence (Otolaryngol Clin North Am 2016;49:1373); propharyngeal surgery can improve OSA of palate/tonsils are obstructive source (Pediatrics 2017;139:e20163314)
Referral: If intolerant of CPAP/BiPAP or sx do not improve → ENT
| Dry mouth | Rx: Nasal mask |
| Dry eyes | Rx: Check for mask fit/leaks |
| Soreness or skin irritation | Rx: Check mask fit, mask cleanliness |
| Claustrophobia | Rx: Check mask fit, use nasal mask, have get used to mask with machine off |
| Sensation of suffocation or intolerance of pressure | May be caused by poor mask fit, leaks
Rx: Check for mask fit/leaks consider BiPAP or APAP, pressure relief |
| Nasal problems (dry nose, congestion, postnasal drip) | Rx: Heated humidification, nasal corticosteroid or saline, if no improvement ENT referral to eval for polyps, deviated septum |
| Abdominal bloating | More common with full face mask Rx: Nasal mask, BiPAP |
OBESITY HYPOVENTILATION SYNDROME (OHS)
Diagnostic Criteria: Obesity (BMI >30 kg/m2) + awake alveolar hypoventilation (PaCO2 >45 mmHg) + sleep-disordered breathing + exclusion of other causes of hypercapnea
Epidemiology: 85–90% have coexisting OSA, ↑ prevalence w/↑ BMI
(Chest 2007;131:1678); assoc w/ ↑ CV mortality when compared to similarly obese w/o OHS (Chest 2016;149:756)
Typical presentation: S/sx: Similar to OSA + dyspnea on exertion; may have s/sx of pHTN and R-sided HF, hypoxia when awake, ± plethoric complexion from polycythemia; labs may include ↑ serum bicarb (compensatory metabolic alkalosis), ↑ HCT
Differential diagnosis includes severe COPD, ILD, chest wall disorders such as kyphoscoliosis, neuromuscular disorders
Evaluation: if suspicion for OHS (obese, OSA, any sx), screen with serum bicarbonate; if elevated → ✓ ABG, PFTs (may be restrictive pattern 2/2 obesity), sleep PSG, CXR (r/o diaphragmatic paralysis), ECG (eval for RAA, RVH), TTE (eval for RVH) ± RHC (eval for pHTN)
(Am J Med 2004;116:1; Chest 2007;131:1678)
Treatment: OSA behavioral tx (wt loss, avoiding sedatives, treating comorbid conditions); CPAP or BiPAP (CPAP okay if maintains adequate ventilation); may also require supplemental oxygen, surgical intervention (incl bariatric surgery; see “Obesity”)
Background (NEJM 2000;343:1715)
Definitions: Subacute cough: 3–8 wk; Chronic cough: >8 wk
Epidemiology: Cough is common symptom-based visit complaint
(NHAMCS 2010, cdc.gov)
Pathophysiology: Cough receptors found in airways, lung parenchyma, tympanic membranes, esophagus, & pericardium; cough is reflex w/ cortical control (may be initiated or suppressed voluntarily); cough mechanism involves diaphragm, glottis, & muscles of expiration Etiology: Varies by duration, can include airway (upper airway cough syndrome [UACS]), HEENT, GI, and CV causes
Evaluation (Chest 2006;129:S1; AFP 2011;84:887)
General approach: Hx/exam to screen potential etiologies; if none discovered → trial of empiric tx for either UACS (upper airway cough syndrome), asthma, or GERD
History: Often nonspecific; ask about onset (post-URI), duration, triggers (after meals—GERD, allergens—asthma); Red flags: Wt loss, hemoptysis, systemic sx
Assoc sx: Postnasal drip, sinusitis, hoarseness, reflux sx, edema PMHx: Atopy, GERD, CHF, immunocompromise, CA, TB exposure/RF
Meds/toxins: ACEI, βB, smoking status/exposure, occupational/environmental exposures
Physical exam: VS: Incl SaO2, HEENT: Auditory canal foreign body, nasal polyps (asthma), cobblestoning (UACS); Pulm: wheezes, crackles; Cardiac: volume overload, valvular disease; Extremities: clubbing
Diagnostics: If dx not suggested by above (e.g., ACEI) → CXR; given
that most chronic cough 2/2 GERD, UACS, or asthma, may be deferred
in nonsmokers until failure of 1st-line empiric tx; further studies (PFTs, CBC, sinus films) as per Ddx (below)
Differential Diagnosis (Lancet 2008;371:1364; NEJM 2000;343:1715)
Subacute cough: Postinfectious cough (48%), infectious sinusitis (33%), asthma (16%) (Chest 2006;129:1142; NEJM 2006;355:2125)
Postinfectious cough: Respiratory tract infection → postnasal drip, tracheobronchitis; resolves w/o tx; average duration of bronchitis-associated cough is 24 d
Sinusitis: See “Sinusitis”
Chronic cough: Often multifactorial; may require tx of multiple causes
| Selected Causes of Chronic cough | |
| Etiology | Management/Notes |
| Smoking | Tx: Smoking cessation; see “Tobacco Use” |
| ACEI | Sx can occur 1 wk–6 mo after starting Rx; cough resolves w/in 2–4 wk of discontinuation of Rx |
| UACS (34%) | Allergic or nonallergic rhinitis, sinusitis Tx: See “Allergic Rhinitis” |
| Cough-variant asthma (28%) | Dx: PFTs (for cough, may start w/ trial of empiric SABA tx)
Tx: See “Asthma” |
| GERD | Dx/Tx: Empiric trial of PPI; see
“Gastroesophageal Reflux Disease” |
Other: COPD, bronchiectasis, eosinophilic bronchitis (dx’ed w/ induced sputum, rx w/ ICS), B. pertussis (see “URI and Influenza”), CHF, ILD, bronchogenic CA, metastatic CA, mediastinal or hilar tumors, allergic alveolitis, lung abscess, EGPA, sarcoidosis, TB, fungal pneumonia (e.g., Cryptococcus), hypersensitivity pneumonitis, allergic bronchopulmonary aspergillosis, habitual cough, foreign body, irritation of external auditory meatus, recurrent aspiration
Management
Figure 13-1. Chronic cough management
When to Refer
If red flags present or sx persist despite empiric tx for common problems, referral to pulmonology for consideration of bronchoscopy/further studies
Background & Evaluation (AFP 2015;91:243; Chest 1997;112:440)
Definition: Blood (mixed w/ sputum or pure blood) expectorated from airway; “massive hemoptysis” defined variably but generally >400 cc/24 h → ED
General approach: Determine source & amount of blood; hx/PE to guide w/u
History: Ask about onset; attempt to quantify blood (frank blood vs. blood-tinged sputum)
Assoc sx: Fever, SOB, cough, respiratory infection, nosebleed, vomiting, epigastric pain Ddx: pseudohemoptysis may be due to ENT (epistaxis), oropharynx (gingivitis, dental disease), or GI (hematemesis) causes PMHx: COPD or other lung disease, immunocompromise, autoimmune disease, CHF, coagulopathy (anticoagulants, liver disease), TB exposure/risk factors, smoking
hx, malignancy (lung or other primary), travel hx
Labs: Consider CBC, coags, further labs as dictated by eval Imaging: Chest CT w/ contrast; further studies as dictated by eval Bronchoscopy: Low threshold to refer
| Selected Differential Diagnosis of Hemoptysis (AFP 2005;72:1253) |
| Airway disease: Bronchitis (most common, 26%), bronchiectasis (i.e., CF); S/sx: Chronic/subacute cough & sputum which turned bloody/blood-streaked Dx: Consider resp viral panel, bronchiectasis w/u, sputum gram stain/culture if suspect bronchiectasis flare |
| Neoplasm: Primary lung cancer (23%), metastasis to lung (melanoma, breast, colon, RCC), bronchial carcinoid, Kaposi sarcoma S/sx: Smoking hx, elderly, wt loss, dry cough, known nonlung malignancy, HIV⊕
Dx: Consider sputum cytology, referral for bx |
| Infection: PNA (10%, often staph, pseudomonas, aspergillus), lung abscess, TB (8%) S/sx: Cough w/ purulent sputum, fevers, chills, wt loss, HIV⊕, immunosuppression Dx: Sputum gs/culture (± AFB), fungal markers, likely referral for bronchoscopy; suspicion of TB requires resp isolation during w/u (see “Tuberculosis”) |
| Increased pulmonary venous pressure: PE, CHF, mitral stenosis S/sx: Dyspnea, hypoxemia, cardiac hx, high risk for DVTs Dx: TTE, consider RHC, see “DVT/PE,” likely → ED/inpt |
| Inflammatory/vasculitic: Vasculitis or pulm-renal syndromes (granulomatosis w/ polyangiitis, Behçet, Goodpasture, SLE pneumonitis), diffuse alveolar hemorrhage (ARDS, cocaine, idiopathic pulm hemosiderosis) S/sx: As per syndrome: Systemic sx, renal failure/CKD, sinus sx, autoimmune hx Dx: ANCA, anti-GBM, UA/urine sediment, BUN/Cr, ANA, anti-dsDNA, anti-Smith, tox screen; referral for bronchoscopy w/ BAL vs. → likely ED/inpt |
| Other: Vascular (AVM, bronchovascular fistula; usually p/w massive hemoptysis); trauma, foreign body, postprocedure; typically → ED |
Management
Treatment: Aimed at underlying etiology
Reverse any existing coagulopathy if there is no contraindication Referral: Massive hemoptysis, hemodynamic instability, or new hypoxemia → ED; any other persistent or chronic hemoptysis, abnl chest CT, or dx uncertain → pulm
Figure 13-2. Management of nonmassive hemoptysis
Background (Chest 2013;143:s93)
Frequently encountered incidentally during chest CT for other causes; recommendations range from no f/u, to interval f/u w/ repeat chest CT, to biopsy; management strategy and communication of risks to pts key role of PCPs
Definitions: Via radiographic characteristics
Solitary pulmonary nodule (SPN): Intraparenchymal lung lesion <3 cm in diameter, not assoc w/ atelectasis or adenopathy Ground glass nodule (GGN): Area of ↑ parenchymal attenuation but with preservation of underlying lung structures, such as airways and vasculature Subsolid nodule: Mixed GGN and solid nodule
Indeterminate: Nodules do not have a clearly benign appearance Size: Nodules <8 mm have lower likelihood of malignancy (Chest 2007;132:108S); lesions larger than 3 cm are termed “lung masses,”
presumed malignant (Chest 2003;123:89S)
Epidemiology: >20% prevalence w/ healthy volunteers (Lancet 1999;354:99) higher in other populations (AJRCCM 2012;185:363)
Etiology: Benign: Nonspecific granuloma > hamartoma, infectious granuloma (Aspergillosis, Cocci, Cryptococcus, Histo, TB); Malignant: Adenocarcinoma, squamous cell, undifferentiated NSCLC, small cell, bronchioloalveolar cell, metastases
Malignancy risk factors: Nodule: Diameter, spiculation (2–2.5x ↑ risk), upper lobe location; Patient: ↑ age, smoking hx (highest: current smokers; pts who quit >7 y ago now low risk), hx extrathoracic CA >5 y before nodule detection, asbestos exposure
Evaluation (NEJM 2003;348:2535)
General approach: Determine if pt high-or low-risk for malignancy based on validated tool (below); use surgical candidacy & pt preference to dictate surveillance strategy; always review prior imaging Probability of malignancy: Should be calculated w/ validated tool, such as Mayo Clinic model (Arch Intern Med 1997;157:849); n.b. this may underestimate risk at low values & test characteristics improved by adding PET (Chest 2005;128:2490); clinical calculator online at reference.medscape.com/calculator/solitary-pulmonary-nodule-risk; consider Brock Calculator for pts w/ nodule detected on lung CA screening (validated in this population) (NEJM 2013;369:910)
Surgical risk: See “Preoperative Evaluation”
Management
Management options include careful observation, further diagnostic testing, or surgery
Shared decision-making: Discussion of risk/benefits of different strategies appropriate, esp for pts of intermed probability where
advantages of any particular approach less certain; in general, if f/u recommended (incl CT) below, >1% risk of malignancy
Fleischner surveillance criteria (below) are for incidental nodules, not those detected via lung cancer screening or those found in immunosuppressed or pts w/hx of malignancy
Surveillance: Done w/ repeat chest CT; generally indicated if low
pretest probability
| Fleischner Criteria for Solid Nodule Surveillance (Rad 2017;284:228) | ||
| Nodule Size | Low Risk | High Risk |
| <6 mm | Not indicated | Consider at 12 mo (optional) |
| 6–8 mm | 6–12 mo, then consider at 18–
24 mo |
6–12 mo, then at 18–24 mo |
| >8 mm | 3 mo or tissue sampling | 3 mo, PET/CT, or bx |
| Multiple nodules | ||
| <6 mm | Not indicated | Consider at 12 mo (optional) |
| 6–30 mm | 3–6 mo, then consider at 18–
24 mo |
3–6 mo, then at 18–24 mo |
| Fleischner Criteria for Subsolid Nodule Surveillance (Rad 2017;284:228) | ||
| Nodule Type | Management | Remarks |
| Solitary pure GGN ≥6 mm | 6–12 mo, then q2y until 5 y | No f/u if <6 mm unless ↑susp, then at 2,4 y; if ↑ in size or develops solid component, consider resection |
| Solitary, part-solid nodule ≥
6 mm |
3–6 mo, if unchanged & solid component <6 mm, q1y for 5 y | No f/u if <6 mm, part-solid nodules w/solid component
>6 mm are highly suspicious |
| Multiple subsolid nodules
<6 mm |
CT 3–6 mo; if stable, consider repeat at 2, 4 y | Usually benign; consider 2, 4 y if pt at ↑ risk |
| Multiple subsolid nodules
≥6 mm |
CT 3–6 mo; then manage based on most suspicious nodule(s) | |
Further diagnostics: Generally indicated if intermediate pretest probability for CA
PET Imaging: Se/Sp 87/83 for malignancy, nodules <1 cm cannot
accurately be evaluated by PET (Lung Cancer 2004;45:19) CT-guided FNA (90% Se, 4–18% risk of PTX, best for peripheral lesions) Bronchoscopy (best for central lesions) (AJRCCM 2012;185:363–372)
Surgical diagnosis/treatment: Generally indicated if high pretest probability for CA VATS, traditional thoracotomy, lobectomy
Multiple nodules: Higher number of nodules (>4) may be assoc w/↓ risk of lung CA (more likely to be benign etiology); surveillance guidelines as above; use most suspicious nodule as guide to
management (Rad 2017;284:228)