Factors Associated With Outcomes of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Figures & data

Table 1.  Clinical Presentation of Acute Exacerbation of COPD

Medical history and signs of severity of exacerbations of COPD
Medical history	Signs of severity
• Duration of worsening or new symptoms.	• Use of accessory respiratory muscles.
• Number of previous episodes (exacerbations/hospitalizations).	• Paradoxical chest wall movements.
• Present treatment regimen.	• Worsening or new onset central cyanosis.
	• Development of peripheral edema.
	• Hemodynamic instability.
	• Signs of right heart failure.
	• Reduced alertness.

Table 2.  Criteria for Hospitalization for a Patient with an AECOPD

Indications for hospital assessment or admission for exacerbations of COPD
• Marked increase intensity of symptoms, such as sudden development of resting dyspnea.
• Severe background COPD.
• Onset of new physical signs (e.g., cyanosis, peripheral edema).
• Failure of exacerbation to respond to initial medical management.
• Significant comorbidities.
• Newly occurring arrhythmias.
• Diagnostic uncertainty.
⩽̸ Older age.
• Insufficient home support.

*Local resources need to be considered.

Table 3.  GOLD Consensus of ICU Admission for AECOPD

Indications for ICU admission of patients with exacerbations of COPD
• Severe dyspnea that responds inadequately to initial emergency therapy.
• Confusion, lethargy, coma.
• Persistent or worsening hypoxemia (PaO2 < 5.3 kPa, 40 mm Hg), and/or severe/worsening hypercapnia (PaCO2 < 8.0 kPa, 60 mm Hg), and/or severe/worsening respiratory acidosis (pH < 7.25) despite supplemental oxygen and NIPPV.

*Local resources need to be considered. [From Ref. [[34]].]

Table 4.  [GOLD] Consensus for Mechanical Ventilation in Exacerbation of COPD

Indications for invasive mechanical ventilation
• Severe dyspnea with use of accessory muscles and paradoxical abdominal motion.
• Respiratory frequency > 35 breaths per minute.
• Life‐threatening hypoxemia (PaO2 < 5.3 kPa, 40 mm Hg or PaO2/FiO2 < 200 mm Hg).
• Severe acidosis (pH < 7.25) and hypercapnia (PaCO2 < 8.0 kPa, 60 mm Hg).
• Respiratory arrest.
• Somnolence, impaired mental status.
• Cardiovascular complications (hypotension, shock, heart failure).
• Other complications (metabolic abnormalities, sepsis, pneumonia, pulmonary embolism, barotraumas, massive pleural effusion).
• NIPPV failure (or exclusion criteria).

FiO₂: Fractional concentration of oxygen in dry inspired gas.

Table 5.  Definitions of Chronic Obstructive Pulmonary Disease Exacerbations Developed for Studies of Antibiotics

Type	Symptoms	Additional minor symptoms
1	An increase in sputum volume
	An increase in sputum purulence
	An increase in dyspnoea
2	Any two from
	An increase in sputum volume
	An increase in sputum purulence
	An increase in dyspnoea
3	A single symptom from	Sore throat or nasal discharge within past 5 days
	An increase in sputum volume	Fever without other cause
	An increase in sputum purulence	Increased wheezing
	An increase in dyspnoea	Increased cough
	Plus at least one minor symptom	Increased respiratory rate > 20% above baseline
		Increased heart rate > 20% above baseline

The best‐studied definition for COPD exacerbation [AECOPD] is that developed specifically for studies of antibiotics in bacterial exacerbations. There are currently no consensus definition for AECOPD. [From Ref. [[42]].]

Table 6.  Staging of a COPD Exacerbation Based on Health‐Care Utilization

Severity	Level of health‐care utilization
Mild	Patient has an increased need for medication, which he/she can manage in own normal environment
Moderate	Patient has an increased need for medication and feels the need to seek additional medical assistance
Severe	Patient/caregiver recognizes obvious and/or rapid deterioration in condition, requiring hospitalization

It is also crucial to note the severity of the underlying COPD, any Comorbid conditions, and the frequency of exacerbations.

[From Ref. [[35]].]

Table 7.  A Scale for Exacerbation Severity Incorporating Exacerbations Managed at Home and in Hospital

Mild	An exacerbation treated with antibiotics but no systemic corticosteroid. If no blood gases are available the absence of respiratory failure is assumed.
Moderate	An exacerbation treated with parenteral corticosteroids with or without an antibiotic. If no blood gases are available the absence of respiratory failure is assumed.
Severe	Type 1 respiratory failure with hypoxaemia but no carbon dioxide retention or acidosis; Pa,O2 < 8 kPa (60 mmHg) and Pa,CO2 < 6 kPa (45 mmHg)
Very severe	Type 2 respiratory failure, compensated with hypoxia, carbon dioxide, retention but no acidosis; Pa,O2 < 8 kPa (60 mmHg), Pa,CO2 < 6 kPa (45 mmHg) and hydrogen ion concentration < 44 nM (pH > 7.35)
Life‐threatening	Type 2 respiratory failure, decompensated with acidosis and carbon dioxide retention; Pa,O2 < 6 kPa (45 mmHg) and hydrogen ion concentration > 44 nM (pH < 7.35)

Pa,O₂: arterial oxygen tension: Pa,CO₂: arterial carbon dioxide tension.

[From Ref. [[42]].]

Figure 1. Incidence of exacerbations per year/mean related to forced expiratory volume in one second (FEV1) in the placebo arms of three 3‐yr studies. [Reproduced from Ref. [[42]].] The open bars are from the inhaled steroid in obstructive lung disease in Europe [ISOLDE] study [From Ref. [[49]]]; the hatched bar is from the Copenhagen City lung study [From Ref. [[45]]] and the shaded bar is from the European respiratory society study on chronic obstructive pulmonary disease. [From Ref. [[46]].]

Table 8.  Recovery from Exacerbation in PEFR and Total Symptom Score in 91 Patients with 504 Exacerbations

	PEFR (IQR)	Symptoms (IQR)
Median time to recovery, d	6 (1 to 14)	7(4 to 14)
% Exacerbations recovering within 35 d	75.2	86.1
% Exacerbations recovering within 91 d	80.2	90.9
% Exacerbations in which the next exacerbation occurs before complete recovery in PEFR	3.4	1.4
% Exacerbations with indeterminate recovery	9.3	3.1
% Exacerbations that do not recover at 91 d	7.1	4.6

IQR = interquartile range.

*Results are presented as median (IQR).

^†Recovery could not be determined for these exacerbations because of missing data.

[From Ref. [[12]].]

Figure 2. International comparison of the burden of health care utilization due to COPD. [From Ref. [[14]].]

Table 9.  Risk Factors of Exacerbation/Hospitalization

Risk factors for potential intervention in exacerbation/hospitalization for COPD
Modification—unclear	Modification—potential
• FEV1	• Infection‐ bacteria/ virus
• Arterial blood gases	• Reduced physical condition
• Basal metabolic rate	• Dyspnoea
• Disease progression	• Smoking
	• Chronic mucous hypersecretion
	• Comorbidity
	• Psychological factors
	• Health status [quality of life]
	• Withholding of medications

Table 10.  Greater the Prevalence of New Strains Greater the Relative Risk of Exacerbation of COPD

Relative Risk of an Exacerbation According to Whether a New Strain of Bacterial Pathogen was Isolated
New strain	Frequency of exacerbation		P value	Relative risk (95% CI)
	New strain	No new strain
	No. of exacerbations/total no. of visits (%)
Any strain	89/270 (33.0)	213/1385 (15.4)	< 0.001	2.15 (1.83–2.53)
Haemophilus influenzae	38/145 (26.2)	257/1503 (17.1)	< 0.001	1.69 (1.37–2.09)
Moraxella catarrhalis	41/84 (48.8)	261/1571 (16.6)	< 0.001	2.96 (2.39–3.67)
Streptococcus pneumoniae	8/25 (32.0)	294/1630 (18.0)	0.01	1.77 (1.14–2.75)
Pseudomonas aeruginosa	3/22 (13.6)	297/1631 (18.2)	0.38	0.61 (0.21–1.82)

*The relative risk of an exacerbation was for the presence of a new strain in sputum, as compared with its absence. Relative risks were calculated with the use of generalized estimating equations, CI denotes confidence interval.

^†Seven visits were excluded because of simultaneous isolation of new strains of M. catarrhalis (six visits) and P. aeruginosa (one visit).

^‡Two visits were excluded because of simultaneous isolation of new strains of M. catarrhalis.

(From Ref. [[69]].)

Table 11.  Studies on the FEV1 as Associated Factor in Exacerbations in or Hospitalizations for Chronic Obstructive Pulmonary Disease [COPD]

Ref	Year	Size	Subjects	Design	Setting	Statistics	Results	Duration	Outcomes	Country
Decramer [Ref. [[48]]]	1997	57	Severe COPD grouped according to hospitalizations	2 group descriptive comparison	Stable COPD No defined selection criteria	2 group comparison	FEV1 not different between the groups	Cross sectional; descriptive	Health care utilization	Belgium
Collet [Ref. [[29]]]	1997	381	Mild to severe COPD	Randomized double blind control of immunostimulant. Secondary analysis of data	Ambulatory patients	Regression models	More severe FEV1, associated with increased hospitalization	6 months	Acute exacerbations in 6 months hospitalization QOL	Canada
Kessler [Ref. [[28]]]	1999	64	Moderate to severe COPD	Prospective cohort	Stable ambulant COPD	Univariate analysis	FEV1 does not predict hospitalization; PaCO2 & PPa independent predictor,	2.5 years	Time to 1st hosp for exacerbation; clinical & functional ‐ ABG, pulmonary hypertension	France
Niewoehner et al. [Ref. [[51]]]	2000	271	Mod to severe COPD	Randomized control	Hospitalized patients	Univariate & multivaliate analyses	FEV1 & 1st few days predict clinical outcomes	30 days with follow‐up 6 months extension	Primary outcome: 30 day treatment failure	US
Garcia‐Aymerich [Ref. [[32]][[33]]]	a) 2001	172	Mod to severe	a) Case control.	Hospitalized patients	Multivariate analysis	FEV1 independent predictor of admission	1 yr recruitment	Clinical & adherence to medicine, social support, physical activity	Spain
	b) 2003	340		b) Prospective cohort.

Table 12.  Mortality Rates in Hospitalized Patients Reported in Different Studies

Reference	Date	Size of Cohort	Country	Mortality Rate	Period of Follow‐up	Setting	Design
Seneff et al. [Ref. [[9]]]	1995	n = 362	US	24%–30% (in hospital) 59% ICU	1 year	ICUs (multi sites)	Prospective cohort
Connors et al. [Ref. [[5]]]	1996	n = 1,016	US	11% in hospital	2 years	Hospitals (multi sites)	Prospective cohort
				43% 1 yr
				49% 2 yr
Roberts et al. [Ref. [[62]]]	2002	n = 1,373	UK	14% (whole group)	3 months	Hospital (multi sites)	Retrospective audit program
				38% (bed bound)
Almagoro [Ref. [[8]]]	2002	n = 135	Spain	22% 1 yr	2 years	Hospital	Prospective cohort
				35.6% 2 yr
Garcia‐Aymerich [Ref. [[33]]]	2003	n = 340	Spain	29%	1 year	Hospital (multi sites)	Prospective cohort
Groenegewen [Ref. [[10]]]	2003	n = 171	Netherlands	23%	1 year	Hospital	Prospective cohort
				35% (ICU)

Figure 3. Health related quality of life can predict hospitalization and mortality in patients with COPD. (From Ref. [[50]].)

Table 13.  Global Initiative for COPD [GOLD] Consensus for hospital Discharge

Discharge criteria for patients with exacerbations of COPD
• Inhaled β2‐agonist therapy is required no more frequently than every 4 hrs.
• Patient, if previously ambulatory, is able to walk across room.
• Patient is able to eat and sleep without frequent awakening by dyspnea.
• Patient has been clinically stable for 12–24 hrs.
• Arterial blood gases have been stable for 12–24 hrs.
• Patient (or home caregiver) fully understands correct use of medications.
• Follow‐up and home care arrangements have been completed (e.g., visiting nurse, oxygen delivery, meal provisions).
• Patient, family, and physician are confident patient can manage successfully.

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