Towards Rational Prescription of Common Inhaler Medication in the Multimorbid COPD Patient

Figures & data

Figure 1(A) Prevalence of frequent comorbid conditions (panel A)*. *Graphical representation of the comorbidities found in 6 large European studies (see Supplementary Data); lines (I–I) connect the minimal and maximal prevalence rates found in these studies; diamonds (

) are used when the condition is reported in only one study.

Figure 1(B) Visual interpretation of COPD medication recommendations^§. ^§Pneumonia data based on Lipson²⁸ and Papi.²⁷

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid (yellow); LABA, long-acting β₂-agonist (blue); LAMA, long-acting antimuscarinic (green).

Table 1 Initiatives for Withdrawal of Inhaled Corticosteroids in Primary Care

Initiator	Tool	Description
IPCRG	Desktop helper^Citation74	Easy tool developed by the IPCRG to help physicians identifying patients who would benefit from ICS treatment vs those in whom it may not be appropriate, and to provide guidance on how to withdraw ICS. Currently available in English, Spanish and Portuguese.
Sweden	Roadmap for ICS withdrawal	A quick reference document available in Swedish (http://www.naaka.se/images/pdf/Nedtrappning-ICS-vid-KOL-lathund.pdf)
Netherlands	ICS reduction tool^Citation86	Based on the Dutch GP guidelines and the IPCRG desktop helper, adapted for the Dutch situation; includes both identification of overuse and suggestions for monitoring after ICS deprescribing.
Belgium	ICS withdrawal questionnaire^Citation87	Five questions for daily practice developed by academic and non-academic chest physicians to provide guidance on (in)appropriate use of ICS and to train small focus groups of primary care physicians.

Abbreviations: IPCRG, International Primary Care Respiratory Group; ICS, inhaled corticosteroids.

Table 2 Most Important Adverse Events Related to Inhaled COPD Maintenance Treatment

Comorbid Category	Medication
	ICS^Citation13,Citation54	LAMA^Citation13	LABA^Citation13,Citation88
Cardiovascular			Tachycardia Rhythm disturbances (in susceptible patients)
Respiratory	Pneumonia Mycobacterial infection (including tuberculosis)
Nervous system			Tremor
Urinary tract		Urinary symptoms
Metabolic	Increased risk of diabetes Poor control of diabetes Decrease bone density/fractures		Hypokalemia (if combined with corticosteroids or thiazide diuretics)
Skin	Bruising
Vision	Glaucoma Cataract	Glaucoma (if used with face mask)
Oropharyngeal	Oral candidiasis Hoarse voice Dental decline	Dry mouth

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting antimuscarinic.

Table 3 Relationship Between COPD Comorbidities and ICS Treatment

Concomitant Condition	ICS Treatment		Ref
COPD	S	If response to bronchodilator treatment is insufficient, adding ICS may be considered if blood eosinophil counts ≥300 cells/µL or ≥ 100 cells/µL in COPD patients with ≥2 moderate exacerbations* or ≥1 exacerbation requiring hospitalization. Initiation therapy with LABA/ICS may be the first choice in selected COPD patients (symptomatic with frequent exacerbations and blood eosinophil counts ≥ 300 cells/µL). A follow-up treatment in combination with LAMA and/or LABA, in selected patients	[^Citation13]
Asthma	R	LABA/ICS may be first choice in COPD patients with a history of asthma and asthma-COPD overlap	[^Citation13]
Pneumonia	C	Regular treatment with ICS increases the risk of pneumonia, particularly in patients with severe COPD. De-escalation of ICS must be considered.	[^Citation13]
Osteoporosis/fractures	C	ICS have been associated with increased bone loss and fracture risk. Consideration in women.	[^Citation61^–^Citation63]
Diabetes and pre-diabetes	C	ICS, particularly high doses, have been associated with onset and progression of diabetes.	[^Citation65,Citation66]
Bronchiectasis	C	ICS may not be indicated in patients with bacterial colonization or recurrent lower respiratory tract infections.	[^Citation13,Citation84]
Mycobacterial infection (including tuberculosis)	C	ICS, particularly high doses, were shown to increase the risk of tuberculosis.	[^Citation71]

Notes: *Moderate exacerbation: defined as exacerbation treated with short-acting bronchodilators plus antibiotics and/or oral corticosteroids.¹³

, Recommended (green); , Selected patients (yellow); , Caution (red).

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting antimuscarinic.

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