Asthma and COPD Flashcards
1
Q
What is a respiratory disease characterized by recurrent REVERSIBLE obstruction to air flow in the bronchiolar airways?
A
Asthma
2
Q
What are the sx of asthma?
A
Chest tightness, wheeze and cough, together with bronchial hyperresponsiveness
3
Q
What is the most chronic disease in children?
A
Asthma
4
Q
What are considered host factors for asthma?
A
Innate immunity
Genetics
Sex
5
Q
Is asthma more prevalent in males or females?
A
Early life is more prevalent in males then at puberty becomes more prevalent in females.
6
Q
What are the environmental risk factors of asthma?
A
Allergens Respiratory infections Tobacco smoke Air pollution Occupations Diet
7
Q
What is the pathophysiology of asthma?
A
Airflow obstruction Bronchospasm, edema Bronchial hyperresponsiveness (BHR) Airways inflammation Chronic inflammation may lead to airway remodeling
8
Q
What causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing?
A
Inflammation
9
Q
What causes the causes an increase in BHR to a variety of stimli?
A
Inflammation
10
Q
Episodes have ___________ that reverses either spontaneously or with treatment (pertaining to asthma)?
A
Air flow obstruction
11
Q
What are the two phases of asthmatic attacks?
A
Immediate-phase response
Late-phase response
12
Q
What is involved in the immediate-phase response?
A
Occurs on exposure to eliciting stimulus
Consists mainly of bronchospasm.
Bronchodilators are effective in this early phase
13
Q
What is involved in the late-phase response?
A
Several hours later
Consists of bronchospasm, vasodilatation, edema and mucous secretion
Caused by inflammatory mediators and neuropeptides released from axon reflexes
Anti-inflammatory drug action needed for prevention and treatment.
14
Q
What is the clinical presentation of asthma?
A
Diverse clinical presentation- episodes of dyspnea/wheezing, tightness in the chest
Chronic daily sx to only intermittent sx
Intervals b/w sx can be weeks, months, or years
Characterized by recurrent exacerbation and remissions
15
Q
What are the environmental triggers of asthma?
A
Allergens: dust mites, pet dander, cockroaches, pollens, molds, viral URIs
Non-allergic triggers: smoke, acid reflux, weather changes (cold air), exercise, occurs at night, occupational irritants/chemical irritants, drugs
16
Q
What are the co-morbid conditions that are triggers of asthma?
A
Allergic rinitis
Sinisitis
GERD
depression
17
Q
What are the drugs that are triggers of asthma?
A
Cardioselective and non-selective Beta Blockers, Calcium antagonists, Dipyridamole, NSAID’s
18
Q
What is acute asthma?
A
Asthma of sudden onset
Status asthmaticus
Life-threatening acute deterioration of stable asthma
(potentially a fatal ER visit with probable admission)
19
Q
What are the sx of an acute or subactue onset of progressively worsening asthma?
A
Shortness of breath, cough, wheezing, and chest tightness
Can be combination of symptoms
Decreases in expiratory airflow
Quantified by measurements of lung function
–Peak expiratory flow (PEF)- measure how well they are breathing out.
–Forced expiratory volume in 1 second (FEV1)
–More reliably indicate severity than symptoms
–Poorly responsive to usual bronchodilator therapy
20
Q
What is involved in the pathologic process for asthma exacerbation that occurs in 80-90% of patients?
A
Onset- may progress over many hours or days or even weeks before functional deterioration is reached
Progressive inflammatory process
WBCs in the airways (eosinophils)
21
Q
What is involved in the pathologic process for asthma exacerbation that occurs in 10% of patients?
A
Onset- Sudden, less than 6 hours, Hyperacute or rapid onset attack
Pathologic process- Smooth muscle spasm
WBCs in the airways (Neutrophils)
22
Q
For a diagnosis of asthma what do you need to determine?
A
Episodic symptoms of airflow obstruction or BHR are present
Airflow obstruction is at least partially reversible
Alternative diagnoses are excluded
23
Q
What are the methods for establishing diagnosis of asthma?
A
Detailed medical history
Physical exam
Spirometry to demonstrate reversibility
24
Q
What should be on the ddx for wheezing?
A
Differential Diagnosis Allergic rhinitis/sinusitis Foreign body Laryngotracheomalacia Cystic fibrosis Bronchopulmonary dysplasia Heart disease COPD Medications
25
If a bronchodilator is not working and forced expiratory volume isnt improved what should you do?
Consider a different diagnosis besides asthma
26
What should be obtained for the medical history of a suspected asthma patient?
```
Type of symptoms
Pattern of symptoms
Precipitating or aggravating factors
Development of disease and treatment
Family history
Social history
Profile of a typical exacerbation
Impact of asthma on patient and family
Assessment of patient/family’s perceptions
```
27
What are the physical exam findings that increase the probability of asthma?
```
Hyperexpansion of the thorax
Sounds of wheezing
Increased nasal secretion, mucosal swelling and nasal polyps
Atopic dermatits/eczema
Although PE could be normal
```
28
What is forced vital capacity (FVC)?
Total amount of air that can be exhaled
29
What is forced expiratory volume in 1 second (FEV1)?
Volume of air exhaled during the first second
30
What does spirometry involve?
FVC and FEV1
31
What does spirometry establish?
Reversibility
32
What are the goals of therapy for asthma?
To achieve and maintain clinical control
Minimal or no chronic symptoms day or night
Minimal or no exacerbations
No limitations on activities; no school missed
Maintain (near) normal pulmonary function
Minimal use of short-acting inhaled beta-2 agonist (< 2 days/week)
Minimal or no adverse effects from medications
33
What is the approach to effective management of asthma?
Patient Education
Identify and Reduce Exposure to Risk Factors
When do you have the attacks prevent those
Prevention of Asthma Symptoms and Exacerbations
Assess, Treat, and Monitor Asthma
To achieve clinical control
34
What are the long term control (LTC) (maintenance) medications used in asthma?
```
Corticosteroids: inhaled (ICS) and systemic
Long-acting beta2-agonists (LABA)
Leukotriene modifiers
Methylxanthines
Cromolyn
Anti IgE
```
35
What are the quick relief medications used in asthma?
Short-acting beta2-agonists (SABA)
Anticholinergics
Systemic corticosteroids
36
Do inhaled cortical steroids have systemic absorption?
Not as much as oral
37
What are the three major advantages of inhaled therapy?
Deliver drugs directly to the airways
Deliver higher drug concentrations locally
Minimize systemic side effects
38
What are the types of inhalers for asthma?
Metered dose
Breath activated
Powder
Spacers are used in conjunction to make use of inhaler easier
39
What is involved with nebulizers?
Convert a solution of drug into aerosol for inhalation
Used to deliver higher doses of drug to the lungs
Are more efficient than inhalers
Used in hospitals for status asthmaticus and treatment of severe asthma
40
Why do nebulizers have limited use?
Cost
Convenience
Over reliance by the patient
41
Inhaled corticosteroids-MOA
Depress the inflammatory response and edema in the respiratory tract and diminish bronchial hyper-responsiveness.
- -Reduced mucous production
- -Decreased local generation of prostaglandins and leukotrienes, with less inflammatory cell activation (decreased inflammation)
- -Adrenoceptor up-regulation
- -Long-term reduced eosinophil and mast-cell infiltration of bronchial mucosa.
42
Inhaled corticosteroids- ROA
Metered dose inhaler
Oral
IV for severe asthma attack
43
Inhaled corticosteroids- Indications
- Most EFFECTIVE long-term control therapy for persistent asthma
- Only therapy shown to reduce the risk of death from asthma even in low doses
- Often used in combination with β2 agonist or other asthma agents.
44
Inhaled corticosteroids- response to therapy?
- Symptoms improve in 1-2 weeks; max in 4-8 weeks
- FEV1 and peak expiratory flow require 3-6 weeks for max improvement
- BHR improvement in 2-3 weeks; max 1-3 months
* *Note- inhaled corticosteroids must be used regularly to be effective.
45
Inhaled corticosteroids- contraindications and ADRs
Contraindication- caution in growing children
ADRS:
Local
Oropharyngeal candidiasis (Thrush)
Dysphonia
Reflex cough and bronchospasm
Potential systemic effects- not seen if low regular doses are being used
Hypothalamic-pituitary-adrenal suppression
Impaired growth in children
Dermal thinning-Dose Dependant
Osteoporosis and glaucoma
46
What do low to medium doses of ICS in children have no adverse effect on?
Bone mineral density
Subcapsular cataracts
Glaucoma
Clinically insignificant effects on hypothalamic-pituitary-adrenal axis
47
Inhaled corticosteroids- Adverse effects in adults
Bone mineral density
--Data suggest cumulative dose relationship
If risk for osteoporosis consider bone-protecting therapy
Ocular effects
--High cumulative lifetime exposure may increase prevalence of cataracts
--Increase risk of glaucoma if family history
48
How can you reduce the potential for adverse effects in inhaled corticosteroids?
- Using a holding chamber (spacer)
- Rinse mouth (rinse and spit) after inhaler use
- Using lowest dose possible- if controlled on low dose don’t give them medium or high dose
- Using in combination with long-acting beta2-agonists (LABA)
49
What are the medication names of inhaled corticosteroids?
```
Fluticasone (Flovent, Flovent Diskus)
Budesonide (Pulmicort Flexhaler, Pulmicort Respules)
Beclomethasone HFA (Ovar)
Flunisolide (Aerobid, aerobid-M)
Triamcinolone (Azmacort)
Mometasone (Asmenex)
Ciclesonide (Alvesco)
```
50
What are the ICS and LABA combinations?
Fluticasone/salmeterol (Advair Diskus, Advair HFA)
| Budesonide/formoterol (Symbicort HFA)
51
What are the long acting beta2 agonists (LABAs)?
```
Salmeterol (Serevent)
Formoterol (Foradil)
Fluticasone/salmeterol (advair)
Budesonide/formoterol (symbicort)
Arformoterol tartrate (Brovana)
Formoterol fumerate (Perforomist)
```
52
LABA's use
Not a substitute for anti-inflammatory therapy
Not appropriate for monotherapy
Beneficial when added to inhaled corticosteroids
Not for acute symptoms or exacerbations
--20 minutes for onset (salmeterol)- that’s too late
53
LABAs
Tolerance with chronic administration
Partial loss of protective effect against- Methacholine, Histamine, Exercise
Bronchodilator response not decreased
Responsiveness to SABA slightly decreased
54
What is the black box warning associated with Long acting beta 2 agonists (LABA)?
May increase the change of severe asthma episodes, and death when those episodes occur
Trying to get rid of this not entirely accurate.
Taking this drug in combo with a steroid DECREASES risk of death but taking it alone could increase asthma and death.
55
LABA- interactions
- Concomitant use of CYP3A4 inhibitors increase salmeterol plasma levels
- Avoid: Ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin
- -Prolonged QTc intervals
- -Palpitations
- -Tachycardia
56
What are the NHLBI recommendations for a patient with asthma that is not sufficiently controlled with ICS alone?
- Increase ICS doase
- Addition of LABA to ICS
- Daily use of LABA- salmeterol and formoterol
- Do not use for treatment of acute sx or exacerbations
- Do not use as a monotherpapy.
57
What are the Leukotriene receptor antagonists?
Montelukast (Singulair)
Zafirlukast (Accolate)
Zileuton (Zyflo)
58
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- MOA
--Competitively antagonize leukotriene receptors D4 and E4 in the bronchiolar muscle, antagonizing endogenous leukotrienes causing bronchodilation.
Zileuton inhibits 5-lipoxygenase—an enzyme necessary for leukotriene synthesis.
Endogenous leukotrienes are thought to cause airway narrowing which is sometimes seen with the use of NSAIDs.
59
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- ROA and indications
Oral
| Alternative tx of mild persistent asthma
60
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- Contraindications
Pregnancy
Caution in elderly
Zileuton is contraindicated in patients with active liver disease
61
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- ADRs
GI disturbances (stomach pain, heartburn)
HA
Zileuton and Zafirlukast liver toxicity
Zafirlukast and montelukast can increases respiratory infections in elderly patients
62
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- drug interactions
Zafirlukast
Interaction with Warfarin – increase in prothrombin time (~35%)
Food can reduce bioavailability
Take 1 hour before or 2 hours after meals
Zileuton
Theophylline – doubles theophylline concentration
Warfarin – increase prothrombin time
Propranolol- doubles propranolol AUC
63
Do leukotriene receptor antagonists have a black box warning associated with suicide?
No.
| They tried to get this but it wasn't passed due to lack of evidence
64
What are the methylxanthine drugs?
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline
65
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- MOA
Methylxanthine
Appear to increase cAMP levels in the bronchial smooth muscle cells by inhibiting phosphodiesterase, an enzyme which catalyses the hydrolysis of cAMP to AMP. Increased cAMP relaxes smooth muscle, causing bronchodilation
66
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- Route and indications
Oral
Aminophylline-IV in severe asthma attacks
Use- refractory patients and used as monotherapy and combination therapy w/ ICS
67
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- Contraindications
Not recommended in children < 4 years
Cardiac disease
HTN
Hepatic impairment
68
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- drug interactions
--Infrequently used due to narrow therapeutic window, drug-drug interactions and safer alternatives
--Significant drug/disease interactions
Viral illness, CHF, cirrhosis, cigarette smoking,etc
--Significant drug/drug interactions
Cimetidine, macrolides, quinolones, etc
CYP1A2 and 3A4 substrate
69
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- adverse effects
Nausea, irritability, insomnia, headache, vomiting
--Less frequent when dosing is low and slow
Tachyarrhythmias
Ventricular arrhythmias, seizures
Seizures reported with concentrations of 25 mcg/mL
Minor side effects do not always occur before severe, life-threatening effects
70
What are the mast cell stabilizers?
```
Cromolyn sodium (intal)
Nedocromil (tilade)
```
71
Cromolyn sodium (intal), Nedocromil (tilade)- MOA and ROA
Mast stabalizers
stabilize mast cells preventing the release of inflammatory mediators
Route- Inhaled
72
Cromolyn sodium (intal), Nedocromil (tilade)- Indications
Patients pregnancy
73
Cromolyn sodium (intal), Nedocromil (tilade)- ADRs
```
Mast stabalizers
Cough
Transient bronchospasm
Throat irritation
Neocromil has a bitter taste
Note: Must be utilized regularly for several weeks before effects are noted. Not indicated for acute asthma.
```
74
Omalizumab (Xolair)- MOA
Immunomodulator
Recombinant monoclonal antibody that binds IgE on mast cells and basophils limits release of mediators of allergic response
75
Omalizumab (Xolair)- indications
For moderate-to-severe persistent asthma in patients 12 years of age or older who are not controlled on other therapies (not first line therapy Reserved )
76
Omalizumab (Xolair)- Safety profile
```
Black Box Warning for anaphylaxis
Anaphylaxis in 0.1% of patients
May develop after any dose
70% of reactions within 2 hours
May be delayed up to 24 hours
Cost-effectiveness and long-term efficacy unknown at this time
```
77
Systemic corticosteroids-MOA
Decrease inflammation by suppression of migration of leukocytes and reversal of increased capillary permeability.
78
Systemic corticosteroids- indications and ROA
Control chronic symptoms in people with severe asthma
Can be used for maintenence but mainly used for acute asthma
Oral therapy preferred over IV
79
What are the quick relief treatments for asthma?
Bronchodilators
--Short Acting Beta2-adrenoceptor agonist
Albuterol: Ventolin® HFA, Proventil® HFA, Proair® HFA- DOC
Pirbuterol: Maxair®
Metaproterenol
Levalbuterol: Xopenex®- r enantimer of albuterol
80
Beta2-adrenoceptor agonist- MOA
- β2-adrenoceptors are located on the airway smooth muscles and respond to epinephrine.
- Stimulation of β2-adrenoceptors leads to a rise in intracellular cAMP levels and subsequent smooth muscle relaxation and bronchodilation.
- β2-adrenoceptor agonist may also prevent activation of mast cells as a minor effect
- β2-adrenoceptor agonist are potent bronchodilators with little if any β1 stimulating properties.
81
Beta2-adrenoceptor agonist- Indications
Relieve bronchospasm during acute exacerbations
Pretreatment for exercise induced bronchoconstriction
Treat the symptoms of asthma but not the underlying disease.
Does not improve control of symptoms
Alone in mild asthma
Adjunct to corticosteroids
82
Beta2-adrenoceptor agonist- ADRs
Fine tremor
Tachycardia
Hypokalemia w/ high doses- albuterol encourages potassium to go intracellulary
Some patients have increased risk of exacerbations, some have decreased lung function
Does not appear to occur with prn use
Short-acting beta agonist such as albuterol are the only inhaled agents indicated for acute asthma attacks therefore also used as rescue inhalers.
83
What are the anticholinergic (Antimuscarinics)?
Ipratropium (Atrovent)
| Tiotropium (Spiriva, Handihaler)
84
Anticholinergics- Ipratropium (Atrovent), Tiotropium (Spiriva, Handihaler)- indications
- Relief of acute bronchospasm
- Not indicated for chronic therapy
- Ipratropium may provide additive effects to B2-agonists, in acute setting
- Alternative for patients with B2-agonist intolerance
- Treatment of choice for bronchospasm due to B-blockers
85
Anticholinergics- Ipratropium (Atrovent), Tiotropium (Spiriva, Handihaler)- MOA
Parasympathetic vagal fibers provide a bronchoconstrictor tone to the smooth muscle of the airways. Activated by reflex with stimulation of sensory receptors in the airway walls.
Muscarinic antagonists act by blocking muscarinic receptors, especially M3 subtype, which responds to this parasympathetic brochoconstrictor tone.
86
Anticholinergics- Ipratropium (Atrovent), Tiotropium (Spiriva, Handihaler)- Contraindications
Glaucoma
| Pregnancy
87
Systemic Corticosteroids- Indication
- -Important in the treatment of severe acute exacerbations
- -Prevent progression of asthma exacerbation
- -Reduce need for referral to ER and hospitalization
- -Prevent early relapse after emergency treatment
- -Reduce morbidity of the illness
- -More than three courses/year → re-evaluate asthma management plan
88
What do long-term control medications depend on?
Age and asthma severity
89
What is the quick relief medication for EVERY asthma patient?
SABA as needed for sx
Increasing use of SABA or use >2 times a week for symptom control (not prevention of EIB) indicates inadequate control and the need to step up treatment
90
What is the the step wise approach to initial management of asthma for quick relief?
- Short-acting bronchodilator: 2-4 puffs inhaled beta-2 agonist as needed for symptoms
- Up to 3 treatments at 20-minute intervals or single nebulizer treatment
91
What is the the step wise approach to initial management of asthma for step 1 (mild intermittent)?
Symptoms < 2 nights/month; Brief exacerbations
| No daily medication needed; quick relief only
92
What is the the step wise approach to initial management of asthma for step 2 (mild persistent)?
Symptoms > once/wk but < 1/day; >2 nights/month, Exacerbations may affect activity and sleep
Preferred Tx = low-dose inhaled steroids (ICS), prn rapid acting beta-2 agonist
Alternative Tx = cromolyn or nedocromil, leukotriene modifier, or theophylline
93
What is the the step wise approach to initial management of asthma for step 3 (moderate persistent)?
Symptoms daily; > 1 night/wk, Exacerbations may affect activity and sleep, Requires daily use of inhaled short acting beta-2 agonist
Preferred Tx = low dose ICS and long-acting inhaled beta-2 agonist, prn rapid acting beta-2 agonist
Alternative Tx = med or high dose ICS or low dose ICS+ leukotriene modifier or theophylline
94
What is the the step wise approach to initial management of asthma for step 4 (Severe persistent)?
Continuous symptoms, limitation of physical activity
Preferred Tx: Medium or high dose ICS and long-acting inhaled beta-2 agonist or if needed oral glucocorticosteroid
95
What are the risk factors for death from asthma?
- -Previous severe exacerbation- e.g. intubation or ICU admission for asthma
- -Two or more hospitalizations or ≥ 3 ED visits in the past year
- -Hospitalization or ED visit for asthma in past month
- -Use of > 2 canisters of inhaled shortacting β2-agonist (SABA) per month
- -Difficulty perceiving asthma severity or the severity of worsening asthma
- -Low socioeconomic status or inner-city residence
- -Illicit drug use
- -Major psychosocial problems
- -Comorbidities: cardiovascular disease,other chronic lung disease, psychiatric disease
96
How is asthma exacerbation managed for mild exacerbation?
Managed at home
97
How is asthma exacerbation managed for more severe exacerbation?
Unscheduled office visit
Emergency department (ED) visit
Hospital admission
Admission to the intensive care unit (ICU)
98
What are the symptoms (Subjective measures) of asthma?
Anxious
Dyspnea, SOB
Chest tightness / burning
99
What are the signs (objective measures) of asthma?
Vital signs: tachycardia, tachypnea
Wheezing
If severe obstruction may not hear any wheezing
Dry hacking cough
Pale/cyanotic skin
Supraclavicular and intercostal retractions
100
What are the signs of hypoxemia associated with asthma?
Decreased oxygen saturation of blood hemoglobin (↓ SaO2)
Decreased partial pressure of blood oxygen (↓ PO2)
Mixed respiratory and metabolic acidosis if severe exacerbation
101
What are the lung function tests?
Decreased PEF or FEV1
102
What are the treatment goals of asthma?
Correction of significant hypoxemia
Rapid reversal of airflow obstruction
Reduction of the likelihood of relapse of the exacerbation or future recurrence of severe airflow obstruction by intensifying therapy
103
What is the initial management of asthma that can be done at home?
- -Teach patients how to monitor signs and symptoms so they can recognize early signs of deterioration and take appropriate action
- -Provide written action plan
- -Daily medications
- -Self-adjustment for acute symptoms
104
Who is COPD found in?
Mainly in long-standing smokers, or occupation-related long-term exposure to substances such as coal dust, asbestos, ect
105
What is COPD associated with?
Bronchitis and emphysema
106
What gives some relief from COPD?
Bronchodilators and anti-inflammatory
| Long-term oxygen therapy also utilized
107
What is the pathophysiology of COPD?
- Inflammation in the peripheral airways and lung parenchyma.
- At the site of lung destruction, macrophages activated by cigarette smoke and other irritants release neutrophil chemotactic factors. Activated macrophages and neutrophils release proteases that break down connective tissue in the lung parenchyma leading to emphysema and mucus production. Cytotoxic T cells contribute to destruction of alveolar walls through release of porphyrins and TNF-α.
108
Define chronic bronchitis?
- Associated with chronic or recurrent excess mucous secretion into the bronchial tree
- Cough that occurs on most days during a period of at least 3 months of the year for at least 2 consecutive years.
109
Define emphysema?
- Abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles
- Accompanied by destruction of their walls, without obvious fibrosis
110
Oxygen
Administered to any patient in respiratory distress except COPD patients who retain CO2. Caution should be used in these patients not to administer too much O2 to depress their respiratory drive.
It increases alveolar oxygen tension and decreases the work of breathing necessary to maintain arterial oxygen tension.
111
What can be used for COPD therapy?
- Anticholinergic agents (DOC in COPD) and beta-2 agonists are foundation of therapy
- -Increase airflow, alleviate symptoms, decrease exacerbation of disease
- -Combo of albuterol and ipratroprium (Combivent) provides greater bronchodilation than either drug alone
- -Inhaled steroids restricted to patients with moderate to severe reduction in airflow in which optimal bronchodilator therapy has failed
- -Addition of long-acting beta-2 agonist (salmeterol, formoterol) improves lung compared to either beta-2 agonist or steroid alone
- -Antibiotics are also used to reduce hospitalizations and to provide better resolution of symptoms in acute exacerbation of COPD
112
When are antibiotics used for COPD?
When 2 of the 3 symptoms are present:
Increased dyspnea
Increased sputum volume
Increased sputum purulence
