Obstructive Lung Disease Flashcards
What does IL-4 do?
directs B lymphocytes to synthesize IgE
What does IL-5 do?
regulates eosinophil production and maturation
What does IL-13 do?
leads to airway eosinophilia, mucous gland hyperplasia, airway fibrosis and remodeling
What are the primary T lymphocytes involved in the pathogenesis of asthma?
Th2 CD4+ T lymphocytes
A 22-year-old male is seen for evaluation of his asthma. He was born at a gestational age of 42 weeks by planned cesarean section to a 19- year-old mother. During pregnancy his mother took herbal pills containing vitamin K. Which of these perinatal factors is associated with the development of childhood asthma?
Delivery by cesarean section. Prematurity (birth between 23-27 weeks gestational age), neonatal jaundice, and prenatal exposure to maternal smoking are other risk factors. Maternal age and vitamin K use have not been shown to be risk factors.
There is no gold standard for the diagnosis of asthma. It is a clinical diagnosis based on history, patient characteristics, physical findings, and the results of other evaluations.
New-onset asthma, although possible, is rare in older adults. The majority of cases are diagnosed in childhood, with most of the remaining cases diagnosed in their teens and twenties.
Baseline spirometry should be obtained in all patients with a suspected diagnosis of asthma.
Spirometry can be normal in a patient with asthma.
Absolute contraindications to bronchoprovocation testing?
SMUK:
Severe airflow limitation (FEV1 < 50% predicted or < 1 L)
Myocardial infarction or stroke in last 3 months
Uncontrolled hypertension (systolic blood pressure > 200 mm Hg or diastolic blood pressure > 100 mm Hg)
Known aortic aneurysm
A false positive bronchoprovacation test can occur in patients with?
ABCs
Allergic rhinitis Bronchitis
Congestive heart failure, COPD
cystic fibrosis
Total serum IgE levels should be measured in patients with moderate-to- severe persistent asthma who are being considered for omalizumab therapy or in patients suspected of having ABPA.
A 55-year-old patient with asthma had three episodes of fever with worsening dyspnea as well as sputum production with brownish mucus plugs in the last 2 months. Chest radiographs show fleeting infiltrates and an HRCT shows central bronchiectasis. Serum IgE levels are elevated (1200 ng/mL) with peripheral blood eosinophilia (700/mL).
What is the most likely diagnosis? Which test should be done next?
Allergic bronchopulmonary aspergillosis.
A skin-prick test checking reactivity to Aspergillus fumigatus should be performed.
Medications associated with EGPA:
COIL
Cocaine
Omalizumab
Inhaled glucocorticoids Leukotriene-modifying
agents
The most direct way to establish the diagnosis of exercise-induced asthma is via exercise challenge testing.
In patients with poorly controlled asthma who experience frequent episodes of exercise- induced bronchoconstriction, the most important strategy is to improve overall asthma control.
In the development of Occupational asthma (OA), the most important factor is the intensity of exposure.
In a symptomatic patient with ongoing exposure, normal spirometry, and a negative nonspecific bronchoprovocation test excludes the possibility of Occupational asthma.
The cornerstone of therapy for OA is to avoid further exposure to the sensitizing agent.
After complete avoidance of exposure, OA improves gradually then plateaus after about 2 years.
Reactive airways dysfunction syndrome (RADS) and Irritant Induced Asthma (IrIA) symptoms are not reproduced by inhalation challenge with low levels of offending workplace agents, while symptoms of immunologic OA are reproduced in those conditions.
After complete cessation of exposure, RADS and IrIA usually improve with time, but some patients continue to have symptoms for at least 1 year and residual physiologic abnormalities like bronchial hyperreactivity can last for several years.
What are symptoms that typically begin within 30 minutes to 3 hours following NSAID use:
ABCDEF
Asthma-like symptoms (acute asthma exacerbation)
Bronchospasm and laryngospasm (might be severe enough to require intubation)
Congestion and conjunctival redness
Diffuse abdominal cramps (less common)
Epigastric pain (less common) and edema (usually periorbital)
Facial flushing
The only way to definitively diagnose NSAID sensitivity is via aspirin challenge testing. However, it is rarely used clinically for establishing the diagnosis of AERD. It is mostly performed as a part of a protocol when aspirin desensitization is indicated.
Although other COX-1– inhibiting NSAIDs can be used safely in AERD patients who have been successfully desensitized with aspirin, only subsequent aspirin therapy has been shown to slow the regrowth of nasal polyps and improve asthma symptoms.
Successfully desensitized patients should continue taking 325 mg of aspirin or equivalent dose of another COX-1–inhibiting NSAID daily to maintain their desensitized state.
It is important for patients to understand that medication use is required to control airway inflammation, even in the absence of symptoms.
Never use inhaled long- acting bronchodilators alone in the treatment of asthma. Studies suggest they may increase risk of asthma-related death when not combined with an inhaled corticosteroid.
Anti-IgE therapy is not a first-line therapy for the majority of asthma patients, but it can be considered in patients with atopic asthma refractory to standard therapy.
A history of severe and/or frequent exacerbations puts patients at increased risk for experiencing a fatal exacerbation.
Epithelial cells –> TGFβ –> small airway fibrosis
Macrophages–> LTB4 and IL-8 –> neutrophil and T-cell chemoattractant –> increase d inflammation
What are the primary lymphocytes involved in pathogenesis of COPD?
A: CD8+ cytotoxic T cells
The rate of female deaths from COPD is rising and the deaths per year have exceeded that of men since the year 2000.
AAT deficiency should be suspected in young (<45 years), white nonsmokers with emphysema and imaging showing bullous disease at the lung bases.
Digital clubbing is not typical in COPD and may reflect other disease processes such as lung cancer or interstitial lung disease.
After age 35, nonsmokers can expect to lose up to 30 mL/year in FEV1 while smokers lose close to 60 mL/year.
When a smoker stops smoking, the rate of FEV1 loss again approximates that of a nonsmoker.
GOLD classification uses three ways to identify high- risk patients when categorizing COPD patients:
1) FEV1 < 50% (GOLD III/IV)
2) >2 exacerbations within the previous 12 months
3) one or more hospitalizations for COPD exacerbation.
Predictor of survival in COPD:
BODE
Body mass index: Lower BMI is a poor prognostic marker
Obstruction (FEV1% predicted)
Dyspnea (mMRC)
Exercise (6-minute
walk distance)
A 56-year-old female with COPD describes dyspnea when hurrying on level ground. Post- bronchodilator FEV1 is 45% predicted with no history of exacerbations within the past year. What is the GOLD combined assessment of this patient?
She is GOLD III based on her FEV1 and scores 1 on the mMRC without a history of exacerbations.
The TORCH trial revealed all the following findings except:
A. Salmeterol reduced exacerbations
B. Salmeterol-fluticasone combination reduced exacerbations
C. Salmeterol-fluticasone combination reduced mortality
D. Pneumonia was more likely in patients taking fluticasone
C; salmeterol-fluticasone combination reduced mortality
The UPLIFT trial revealed that tiotropium was associated with all the following outcomes except:
A. Reduction in exacerbations
B. Reduction in the rate of FEV1 decline
C. Reduction in hospitalizations related to exacerbations
D. Improved quality of life
B; reduction in the rate of FEV1 decline
The following inhaled therapies reduce COPD exacerbations: LABA, LAMA, and LABA/ICS
What therapy has been shown to slow the rate of FEV1 decline?
A. LABA
B. LAMA
C. Smoking cessation
D. LAMA + LABA/ICS E. LAMA + LABA
C; smoking cessation
Pulmonary rehabilitation improves all of the following except:
A. Dyspnea,
B. Quality of life,
C. FEV1
D. 6-minute walk distance
C. FEV1
What are the benefits of pulmonary rehabilitation?
BREATH(e) EASY
Breathlessness reduction
Recovery after
exacerbation
Exercise capacity (6-
minute walk, shuttle
walk)
Anxiety and depression
reduction
Training of respiratory
muscles
Hospitalization frequency
and days in hospital decreased
Enhanced efficacy of long- acting bronchodilators
Arm function improvement
and endurance training
of upper limbs
Survival (possible mortality
benefit)
Your quality of life
improvement
A 55-year-old woman with severe emphysema presents for consultation. FEV1 is 38% predicted, DLCO is 38% predicted, and she is on optimal medical therapy. She has completed pulmonary rehabilitation but still has poor exercise capacity. CT of the chest reveals upper lobe-predominant emphysema. What is the recommended treatment?
A. Bullectomy
B. Lung transplantation C. Hospice care
D. Lung volume reduction surgery (LVRS)
D; lung volume reduction surgery (LVRS)
A 55-year-old women, a 25-pack-year ex-smoker, presents with dyspnea when walking on level ground after a few minutes. Her post-bronchodilator FEV1/FVC is 0.62. FEV1 is 59% predicted. She has never been treated for a COPD exacerbation. What should be the initial management of her COPD?
A. ICS + LABA
B. LAMA + LABA C. LAMA or LABA +
pulmonary
rehabilitation D. LAMA only
C; LAMA or LABA + pulmonary rehabilitation
A 67-year-old male sees you for breathlessness when walking at his own pace on level ground. His post-bronchodilator FEV1 percent predicted is 55%. He has been treated for a COPD exacerbation twice within the last year. What GOLD classification is he and what is the recommended initial therapy?
GOLD D; ICS + LABA and/or LAMA
Inhaled corticosteroids are associated with an increased risk of what?
pneumonia in COPD patients.
Viral or bacterial respiratory tract infections are the most common cause of COPD exacerbations.
The single best predictor of a COPD exacerbation is?
A history of COPD exacerbations
Commercially available genotyping can diagnose 20–30 of the most common mutations, which account for > 90% of the most common mutations of CF
Infection with B
cepacia complex is considered a contraindication for lung transplant in many centers because of increased mortality.
Infection with Burkholderia cepacia complex is considered a contraindication for lung transplant in many centers because of increased mortality
What is the most common mutation in CF?
ΔF508 mutation, a class II mutation (due to deletion of a single phenylalanine residue at position 508). It is the most common mutation in CF, affecting 70% of CF patients.
What gene mutation is targeted by ivacaftor?
Ivacaftor, a recently approved CFTR- modulating therapy, targets the G551D CFTR mutation (a class III mutation), found in only about 4% of all CF patients.
Order of inhaled medications: bronchodilator → hypertonic saline → dornase alfa → airway clearance → aerosolized antibiotic.
In patients with CF, chronic infections with what pathogens are associated with accelerated decline in lung functions?
P aeruginosa, B cepacia,
and MRSA
ICS decreases COPD exacerbation risk: Median exacerbation rate was reduced by 25% was shown by which study?
ISOLDE study
LAMA decreases exacerbations in COPD shown in which study?
14% reduction in exacerbations, 4 year study
UPLIFT study
LABA + ICS decreases exacerbations more than ICS or LABA alone shown in which study?
TORCH study
LAMA decreases exacerbations more than LABA shown in which study?
POET-COPD study
LAMA/LABA decreases exacerbations more than ICS/LABA shown in which study?
1680 patients followed over 1 year
FEV1 25-60%; mMRC >2; at least 1 exacerbation in the past 1 year
Effect independent of baseline blood eosinophil count
Higher incidence of pneumonia in ICS group
FLAME study
Triple therapy vs ICS/LABA or LABA/LAMA
52-week trial
8509 patients with mod-very severe COPD
> 1 mod-severe exacerbation in prior year if FEV <50%
> 2 moderate or > 1 severe exacerbation if FEV1 50-65%
ETHIOS study
Triple therapy vs LAMA/LABA and ICS/LABA
52-week trial
10,355 patients with symptomatic COPD; FEV1 <50% and at least 1 mod-severe
exacerbation in prior year; FEV1 50 -<80% and at least 1 severe or 2 moderate
exac.
shown in which study?
IMPACT study
Roflumilast and exacerbations in COPD - shows 13% reduction in exacerbations shown in which study?
REACT trial
When do you use oxygen therapy in stable COPD?
Long-term oxygen therapy increases survival in patients with severe chronic resting arterial hypoxemia (PaO2 < 55 mmHg)
PaO2<55mmHgorSaO2<88%
PaO2<59mmHgorSaO2<89%
with:
EKG evidence of cor pulmonale
Hematocrit > 55
Clinical evidence of right heart failure
When is surgical lung volume reduction for COPD indicated?
survival benefit in upper lobe emphysema/low exercise capacity
What does a bullectomy provide?
Improves dyspnea, lung function, exercise tolerance
When to send a COPD patient for lung transplant evaluation?
Suggested criteria: BODE > 7;
FEV1 <15-20%;
> 3 severe exac past year;
1 acute hyercapnic RF;
mod-severe pulmonary hypertension
What does a bronchoscopic lung volume reduction do in COPD patients?
Improves RV
improves lung function and exercise tolerance
What interventions in COPD reduce mortality?
LABA+LAMA+ICS
Smoking cessation
Lung volume reduction surgery
Long term O2 therapy
NIPPV
Pulmonary rehab
What is the AIR-2 trial and the inclusion criteria?
Bronchial thermoplasty - evaluate safety and effectiveness in pts with severe persistent asthma
- ICS >1000ug BDP equiv + LABA; ± OCS ≤10 mg/day
- At least 2 symptom days in 4-week baseline
- Pre-bronchodilator FEV1 ≥ 60% Predicted !!
- ≤ 8 puffs/24h rescue medication, excluding for exercise
What is the AIR-2 trial and the exclusion crtieria?
Bronchothermoplasty
Exclusion criteria:
- Post-bronchodilator FEV1 < 65% predicted
- ≥ 3 hospitalizations for asthma exacerbations in past 12 months !!
- > 3 respiratory tract infections in the past 12 months
- ≥ 4 pulses of OCS for asthma in the past 12 months
- Chronic sinus disease defined by 5 or more episodes of sinusitis in the past 12 months or continuous symptoms of sinus infection in last 6 weeks
- Uncontrolled GERD defined by a significant increase in therapy in last 6 weeks
- Known sensitivity to medications required for bronchoscopy (eg. lidocaine, atropine, benzodiazepines)
When do you start NIPPV in COPD?
PaCO2 >52 mmHg and pH 7.35
Stable COPD
Long term NIPPV targeted to reduce hypercapnia
Genetic factor in A1AT deficiency?
SERPIN A1 gene mutation
