Inhaled Corticosteroids


Article Author:
Tian Liang


Article Editor:
Jennifer Chao


Editors In Chief:
Chaddie Doerr


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
2/20/2019 11:36:20 AM

Indications

Inhaled corticosteroids (ICS) are the FDA-indicated treatment of choice in preventing asthma exacerbations in patients with persistent asthma. Persistent asthma is classified by symptoms more than two days a week, more than three nighttime awakenings per month, more than twice a week use of short-acting beta-2 agonists for symptom control, or any limitation of normal activity due to asthma. Regular use of these medications reduces the frequency of asthma symptoms, bronchial hyperresponsiveness, risk of serious exacerbations, and improves quality of life. These medications are initiated in a stepwise fashion based on the frequency and severity of the asthma symptoms. Low-, medium-, and high-dose inhaled corticosteroids are available to treat mild, moderate, and severe persistent asthma respectively. If inhaled corticosteroids alone are not adequate in controlling a patient's asthma symptoms, other controller medications such as long-acting beta agonists or leukotriene receptor antagonists also may be started. Asthma controller medications often are used in conjunction with short-acting beta agonists such as albuterol as part of an asthma action plan to address acute and chronic symptoms. [1][2][3][4]

Inhaled corticosteroids also are prescribed off-label (non-FDA approved) for management of chronic obstructive pulmonary disease (COPD). Up to 40% to 50% of patients with COPD receive inhaled corticosteroid therapy. Data suggests that these medications decreased the number of exacerbations and may slow the progression of lung disease. There is, however, minimal impact of inhaled corticosteroids on lung function and mortality. Inhaled corticosteroids are most often used in COPD as an adjunct to long-acting inhaled bronchodilators but may be initiated earlier if there is an asthmatic component in a given patient’s lung disease.

Mechanism of Action

Inhaled corticosteroids have potent glucocorticoid activity and work directly at the cellular level by reversing capillary permeability and lysosomal stabilization to reduce inflammation. The onset of action is gradual and may take anywhere from several days to several weeks for maximal benefit with consistent use. Metabolism is through the hepatic route, with a half-life elimination of up to 24 hours.[5][6][7][8]

Administration

These drugs are administered through the inhalation route directly to their sites of action. This decreases the dose required for the desired effect as it bypasses the first-pass metabolism in drugs taken orally. The reduced systemic bioavailability also minimizes side effects. Inhaled corticosteroids come in liquid capsule formulations that are given through a nebulizer machine, metered dose inhalers (MDI) administered through spacers, and dry powder inhalers (DPI). Advantages and disadvantages of each are as follows:

Nebulizer

  • Advantages: Coordination with the patient not required, high doses possible
  • Disadvantages: Expensive, more time required (10 to 15 minutes per dose), contamination of machine

Metered Dose Inhalers (MDI)

  • Advantages: Less expensive than nebulizers, convenient, faster to use, dose counter
  • Disadvantages: Coordination is essential if not using a mask, pharyngeal deposition, difficult to deliver high doses

Dry Powder Inhaler (DPI)

  • Advantages: Portable, dose counter, less coordination needed compared to MDI
  • Disadvantages: Needs higher inspiratory flow to use effectively, pharyngeal deposition of medication, cannot use in mechanically vented patients

Drug deposition of inhaled corticosteroids in children older than five are similar to that of adults, so the method of administration of ICS in these ages groups should be decided based on patient and family preference. However, toddlers and infants cannot reliably generate a sufficient inspiratory flow rate to use dry powder inhalers, so this method of delivery is not recommended for this age group. It is recommended that young children either use a nebulizer or MDI with mask and spacer to deliver inhaled corticosteroids.

Many different brands of inhaled corticosteroids are available on the market with similar efficacy between the formulations. Widely used inhaled corticosteroids include budesonide, fluticasone, beclomethasone, flunisolide, mometasone, and triamcinolone.

Adverse Effects

Local adverse effects of inhaled corticosteroids include dysphonia, oral candidiasis, reflex cough, and bronchospasm. These adverse effects are less common with low-dose inhaled corticosteroids than with high-dose inhaled corticosteroids. These adverse effects are also mitigated by spacer use when taking the medication via metered dose inhalers.[9][10][11]

Up to 60% of patients report dysphonia while using inhaled corticosteroids. It is due to myopathy of the laryngeal muscles and mucosal irritation, and it is reversible when the treatment is withdrawn. Oral candidiasis (thrush) is another common complaint among users of inhaled corticosteroids. This risk is increased in elderly patients and patients who are also taking oral steroids, high dose ICS, or antibiotics. Laryngeal and esophageal candidiasis also has been described in the literature. It is advised to have the patient rinse their mouth out after ICS use to prevent oral candidiasis. Treatments for candidiasis include clotrimazole, miconazole, and nystatin.

Inhaled corticosteroid use has been associated with a reduction in growth velocity in children with asthma. However, these effects in low doses of inhaled corticosteroids are small, nonprogressive and potentially reversible. Inadequate control of asthma also is associated with reductions in growth velocity, and early intervention with inhaled corticosteroids significantly improves asthma control. Thus, the benefits of ICS use outweighs the risk. Other potential systemic adverse effects of inhaled corticosteroids are rare and/or clinically insignificant, including cataracts, glaucoma, hypothalamic-pituitary-adrenal axis dysfunction, and impaired glucose metabolism. Symptomatic patients who are on long-term, inhaled corticosteroids should be screened for these conditions, or asymptomatic patients on the long-term, high-dose ICS.

There is conflicting evidence on the effect of inhaled corticosteroids on bone metabolism and osteoporosis. High doses of ICS are associated with increased risk of fracture. Adult patients on chronic ICS therapy should undergo bone density measurement. Routine testing of bone density in children is not needed, but supplementation with adequate vitamin D and calcium is recommended.

Contraindications

There are few absolute contraindications to the various inhaled corticosteroids available in the United States. These include hypersensitivity to the medication and severe hypersensitivity to milk proteins/lactose. Dry powder inhalers often contain lactose as a stabilizing agent. Though not intentional, there have been reports of milk protein contamination within lactose-containing medications including dry powdered inhalers. Therefore, in patients with severe milk protein or lactose allergies, DPI asthma medications are contraindicated. Additional contraindications in Canadian labeling include untreated fungal, bacterial, and tubercular infections of the respiratory tract. Inhaled corticosteroids are recommended for treating asthma during pregnancy. Maternal ICS use during pregnancy has not been shown to increase the risk of congenital malformations or impaired fetal growth.

Monitoring

Enhancing Healthcare Team Outcomes

Inhaled corticosteroids are prescribed by many healthcare professionals including the nurse practitioner, primary care provider, pulmonologist, ENT surgeon, allergist and the emergency department physician. It is important to know the adverse effects of inhaled corticosteroids. Patients should be educated about the local adverse effects and how they can be reduced. More important, inhaled corticosteroid use has been associated with a reduction in growth velocity in children with asthma. However, these effects in low doses of inhaled corticosteroids are small, nonprogressive and potentially reversible. Inadequate control of asthma also is associated with reductions in growth velocity, and early intervention with inhaled corticosteroids significantly improves asthma control. Thus, the benefits of ICS use outweighs the risk. 

There is conflicting evidence on the effect of inhaled corticosteroids on bone metabolism and osteoporosis. High doses of ICS are associated with increased risk of fracture. Adult patients on chronic ICS therapy should undergo bone density measurement. Routine testing of bone density in children is not needed, but supplementation with adequate vitamin D and calcium is recommended.


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Inhaled Corticosteroids - Questions

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A patient who is a steroid-dependent asthmatic is started on a beclomethasone inhaler. Which should be part of patient education?



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Which of the following corticosteroids is ineffective as an inhaler but works well when given orally?



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How long after initiation does it take for inhaled corticosteroids to have an effect when administered for asthma treatment?



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A child with asthma is using daily, inhaled corticosteroids for her condition. What is the most common adverse effect of this therapy?



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What is a common complication of using inhalers containing corticosteroids?



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Which of the following is not true about the use inhaled corticosteroids for asthma?



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What is the administration route of fluticasone when used for asthma?



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A 17-year-old male begins inhaled corticosteroid therapy for mild persistent asthma. During the office visit, he is counseled on proper inhaler technique. He also is advised to rinse his mouth and throat with water after each use, expectorating the rinsate. This is intended to prevent overgrowth by which of the following organisms?



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Beclomethasone (oral inhaler) is the active ingredient for which of the following corticosteroid inhalers?



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For which of the following is inhaled flunisolide FDA approved to treat?



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A patient has been given a prescription for his asthma. Upon dispensing the drug, the pharmacist counsels the patient to rinse his mouth with water and to spit out rinse solution. Which of the following asthma medications is most likely to have been prescribed to this patient?



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An asthmatic patient is initiating orally inhaled beclomethasone to control his asthma. Which of the following is a counseling point?



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A patient is being started on an inhaled corticosteroid to improve management of her asthma. Which counseling point should she be given regarding her new medication?



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A 5-year-old girl with asthma presents to your office. She currently only uses albuterol in the management of her condition. Her mother says that she uses her albuterol meter dose inhaler three times per week for shortness of breath with good control of her condition. Her asthma does not cause her to wake up at night. Which of the following medications would be indicated to help control her asthma?



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An 8-year-old male with asthma presents to the emergency department in severe respiratory distress. His heart rate is 140 beats/min and respiratory rate is 45. His oxygen saturation is 88% on room air. On physical exam, he is tired appearing, with bilateral diffuse wheezing on auscultation, and intercostal and supraclavicular retractions. Which of the following medications is not indicated for treating this patient?



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Inhaled Corticosteroids - References

References

Bloom CI,Saglani S,Feary J,Jarvis D,Quint JK, Changing prevalence of current asthma and inhaled corticosteroid treatment in the UK: population based cohort 2006-2016. The European respiratory journal. 2019 Feb 14;     [PubMed]
Griffith MF,Feemster LC,Donovan LM,Spece LJ,Krishnan JA,Lindenauer PK,McBurnie MA,Mularski RA,Au DH, Poor Metered-Dose Inhaler (MDI) Technique Is Associated with Overuse of Inhaled Corticosteroids in COPD. Annals of the American Thoracic Society. 2019 Feb 14;     [PubMed]
Kanda A,Kobayashi Y,Asako M,Tomoda K,Kawauchi H,Iwai H, Regulation of Interaction between the Upper and Lower Airways in United Airway Disease. Medical sciences (Basel, Switzerland). 2019 Feb 11;     [PubMed]
Selby L,Saglani S, Severe asthma in children: therapeutic considerations. Current opinion in allergy and clinical immunology. 2019 Jan 31;     [PubMed]
Rogliani P,Calzetta L,Matera MG,di Daniele N,Girolami A,Cazzola M,Ora J, Inhaled therapies and cardiovascular risk in patients with chronic obstructive pulmonary disease. Expert opinion on pharmacotherapy. 2019 Feb 1;     [PubMed]
Maglione M,Poeta M,Santamaria F, New Drugs for Pediatric Asthma. Frontiers in pediatrics. 2018;     [PubMed]
Ramadan AA,Gaffin JM,Israel E,Phipatanakul W, Asthma and Corticosteroid Responses in Childhood and Adult Asthma. Clinics in chest medicine. 2019 Mar;     [PubMed]
Mahay G,Le Brun M,Taillé C, [Asthma exacerbations in adults: Preventing and treat]. Presse medicale (Paris, France : 1983). 2019 Jan 18;     [PubMed]
Nanda A,Baptist AP,Divekar R,Parikh N,Seggev JS,Yusin JS,Nyenhuis SM, Asthma in the older adult. The Journal of asthma : official journal of the Association for the Care of Asthma. 2019 Jan 18;     [PubMed]
Cates CJ,Schmidt S,Ferrer M,Sayer B,Waterson S, Inhaled steroids with and without regular salmeterol for asthma: serious adverse events. The Cochrane database of systematic reviews. 2018 Dec 3;     [PubMed]
Zhang L,Lasmar LB,Castro-Rodriguez JA, The impact of asthma and its treatment on growth: an evidence-based review. Jornal de pediatria. 2018 Nov 22;     [PubMed]

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