Can Acid Reflux Cause Shortness of Breath?

How Asthma Management Is Changing – What Nurses Need To Know

Respiratory nurse lead Carol Stonham outlines what nurses in primary care need to know about changes in the diagnosis and treatment of asthma, following recently updated UK joint guidelines

In November 2024 a joint UK asthma guideline was published by NICE, the British Thoracic Society (BTS) and the Scottish Intercollegiate Guidelines Network (SIGN). This offers greater clarity in how to diagnose asthma, and an updated, evidence-based approach to treatment.

Prior to this, clinicians had been navigating some conflicting national and international guidelines and strategies, as well as local recommendations. This has often led to difficulty in diagnosing asthma accurately.  In addition, despite increasing availability of different asthma medications and clear recommendations 10 years ago from the National Review of Asthma Deaths, the number of people dying from asthma has barely changed.1

The new guideline offers a chance to offer a standardised, evidence-based approach that respiratory experts believe should improve outcomes for people living with asthma. Anyone diagnosing or managing asthma should be familiar with the new guidelines – this article introduces the main changes, but it is important for nurses to read through the guidelines for more detail.

Stepwise approach to diagnosis

The diagnosis of asthma has always relied heavily on a history in keeping with a likely diagnosis of asthma, and this has not changed. However, the new guidelines recommend only one positive objective test is required to confirm the diagnosis – rather than two, as recommended in previous NICE guidelines and consequently in QOF. (This is one of the areas where NICE and BTS/SIGN asthma guidelines previously diverged.)3,4

The choice of testing follows a sequential approach. The initial test should be measurement of fractional exhaled nitric oxide (FeNO) levels, or alternatively in adults there is now the option to measure blood eosinophil levels.

The stepwise approach to diagnosis in adults can be summarised as:

Measure blood eosinophil count or FeNO level in adults with a history suggestive of asthma. An eosinophil count above the laboratory reference range, or a FeNO above 50ppb, is enough to confirm diagnosis.

If the blood eosinophil or FeNO is negative, the next diagnostic test should be spirometry with bronchodilator reversibility (BDR). An increase in FEV1 of 12% or more and 200ml or more post-bronchodilator supports a diagnosis of asthma. The guidelines recognise that there may be a delay in accessing spirometry or BDR, however.

If spirometry is not available, or delayed, peak expiratory flow (PEF) variability can be used as an alternative. PEF should be measured twice daily for 2 weeks. Mean variability of 20% or more can be interpreted as a positive test confirming diagnosis.

If asthma not confirmed by any of the above tests, then refer for bronchial challenge testing.

The guidance reminds us to consider occupational asthma, although this aspect is not covered in detail. Further information and guidance should be sought from the BTS Occupational Asthma Clinical Statement.5

In children aged 5-16, the stepwise approach is:

The initial test to support a diagnosis in children with a history suggestive of asthma is a FeNO test. A result above 35ppb is positive. Again, this test alone is appropriate to confirm a diagnosis.

If the result is negative (below 35ppb), further testing is required using spirometry with BDR. An improvement of 12% post-bronchodilator confirms diagnosis.

If spirometry is not available, or delayed, PEF variability is also appropriate for children, with 20% or more variability indicating a positive diagnosis.

If these tests fail to confirm diagnosis the child will need either skin prick testing to house dust mite or a blood test for IgE. Sensitisation to house dust mite or raised IgE along with raised blood eosinophils (above 0.5 x109 per litre) confirm the diagnosis. If testing remains negative, a referral for specialist opinion and consideration of challenge testing is required.

In any age group, alternative diagnoses should be kept in mind, especially if all tests fail to confirm asthma.

New stepwise treatment approach

The guidelines have made a big change to the management of asthma and now align more closely with international Global Initiative for Asthma (GINA) recommendations.6

The striking difference most nurses will notice is move away from prescribing short acting beta-agonists (SABAs) in the treatment algorithms.

NICE emphasises that SABAs should not be prescribed at all without a concomitant prescription of an inhaled corticosteroid (ICS), and they are no longer recommended even in combination with an ICS in newly diagnosed patients.

Treatment in people aged 12 and over

In this group treatment recommendations can be summarised as follows:

For patients with minimal symptoms, a 2-in-1 combination inhaler, including the long-acting beta agonist (LABA) formoterol and an inhaled corticosteroid (ICS), is recommended for as-needed symptom relief. This is referred to as an AIR (anti-inflammatory reliever) regimen. The formoterol acts as rapidly and effectively as a SABA in treating acute symptoms. So when used as a reliever inhaler, the ICS-formoterol both relieves acute symptoms and reduces underlying inflammation. This approach also effectively titrates the preventer ICS medication in line with asthma symptoms, helping to reduce future symptoms and risk (unlike SABA use, which allows untreated inflammation to escalate). Note that currently only a few inhalers are licensed to be used in this way.

If the person is more symptomatic, or has experienced an exacerbation, low-dose MART (maintenance and reliever therapy) should be prescribed, using a formoterol-containing ICS combination. Many of the formoterol containing combination inhalers are licensed to be used as a MART regimen. This regimen involves using the combination inhaler twice-daily as treatment, and as-needed for symptom relief.

If poor asthma control is experienced despite the low-dose MART regimen, after checking the basics of asthma care (eg, inhaler technique, adherence, smoking, co-morbidities, triggers), a move to a moderate-dose MART regimenis recommended. This means using a formoterol-ICS combination inhaler with an increased dose of ICS.

If, despite moderate dose MART treatment, the person continues to experience regular asthma symptoms or exacerbation, another new recommendation is to check their FeNO level and eosinophil count, which can then help guide treatment decisions.

A normal FeNO (below 50ppb for adults) and within-range eosinophil count suggests the inflammation is under control, so a third medication can be added. This could be a long-acting muscarinic antagonist (LAMA). Note that triple therapy inhalers combining a LAMA with formoterol and ICS are not licensed for use as MART; patients can instead be prescribed a separate LAMA inhaler alongside moderate-dose MART. The other option is to add in an oral leukotriene receptor antagonist (LTRA) such as montelukast. Whichever therapy is added in, it is important to review the patient to further titrate treatment, or swap to the alternative, or if this fails refer to a specialist.

If either the FeNO or eosinophil result is raised, the patient should be referred to a specialist for consideration of a biologic asthma medication.

Treatment in children aged 5-11 years

In children aged between 5 and 11 years the pathway can be summarised as:

Start by prescribing a paediatric low-dose ICS with a separate SABA for symptom relief – what has until now been the traditional treatment.

If, despite this, the child's symptoms are not controlled, then prescribe a paediatric low-dose MART regimen, provided the child is able to manage this. The dilemma here is that there are currently no inhalers licensed for MART regimens in this age group, so it would be prescribed off-label, but following guideline recommendation. Consultation notes will need to reflect this. NICE notes that evidence supporting low-dose MART in children aged 5-11 is based on use of a dry powder inhaler.  In this age group it is worth considering whether a SABA and spacer should also be prescribed, as they may not be able to actuate a dry powder device in an emergency situation.

Escalate treatment in those who continue to have symptoms (having first checked inhaler technique, adherence, and trigger exposure) to a paediatric moderate-dose MART regimen. If this still does not control symptoms, the child should be referred for specialist advice.

If the child is unable to manage a MART regimen, consider adding a leukotriene receptor antagonist (LTRA) to the low-dose ICS with separate SABA and review 8-12 weeks later. If ineffective the LTRA should be stopped.

If still uncontrolled, offer a twice-daily ICS and long-acting bronchodilator agonist (LABA) combination inhaler, with a separate SABA for symptoms (with or without LTRA depending on response). It can be escalated to a paediatric moderate-dose ICS and LABA combination inhaler, again with a separate SABA for symptoms. Further changes beyond this should be on the recommendation of a specialist.

For more detailed summaries of the treatment pathways see the NICE treatment summary flow-charts for people aged 12 and over and for children aged 5-11.

Switching existing asthma patients to new treatments

Patients on SABA only

The cohort of people that will require review and likely a change in treatment is those using SABA therapy alone. In previous iterations of the BTS/SIGN and NICE guidelines a SABA-only regimen was recommended for mild asthma, so it is likely there is a considerable number of these patients in every practice. The guidelines now state that we should not prescribe SABA in people of any age with asthma, without a concomitant prescription of ICS.

Searches on clinical record systems will quickly identify this cohort.  If truly asymptomatic most of the time, these patients should be offered AIR therapy (combination inhaler including formoterol and ICS, used for as-needed symptom relief). Patient education, as always, is vital for patients to engage in their care and accept change. To help the patient understand why they need to switch to the combination inhaler, explain what asthma is, with inflammation at its core, how inhalers work, and why not treating inflammation is a risky strategy.  Many patients will have received advice from clinicians about the importance of always carrying their blue inhaler so will need to understand the rationale and importance of switching. An explanation that the bronchodilator is not being changed but is being 'upgraded' usually reassures patients.

 

Patients on any regimen that includes ICS

If patients on any ICS containing regimen for previously diagnosed asthma are stable and symptom-free they do not necessarily need to be moved onto one of the new treatment pathways. However, it is important to remember many people with asthma normalise their symptoms and adjust activity and lifestyle to accommodate it. At review, make sure to ask probing questions to ascertain if a person is truly asymptomatic and well.

For those with symptoms that are not on a MART regime, the guidelines recommend moving to a MART regime without reducing the dose of ICS.

If the person is on a high-dose ICS and symptomatic, a specialist opinion should be sought.

Remember always that people have the right to be involved in discussions and make informed decisions about their care. NICE reiterates this and refers to the NICE Making Decisions About Your Care document.7

Carol Stonham is a Primary Care Respiratory Society UK Trustee, vice chair of the Taskforce for Lung Health, and co-clinical lead for the NHS England South West respiratory network

References

Royal College of Physicians. Why asthma still kills; the national review of asthma deaths (NRAD). 2014

NICE. Asthma: diagnosis, monitoring and chronic asthma management (BTS, NICE, SIGN). [NG245] 27 November 2024

British Thoracic Society/Scottish Intercollegiate Guideline Network (2019) Guideline for the management of asthma.

(2017) Asthma NG 80. Archived and replaced by NG 245

British Thoracic Society. BTS Clinical Statement on Occupational Asthma. 2022

Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2024

Making decisions about your care.

Further reading and resources

RightBreathe. Inhalers

PCRS UK. Asthma Guidance and Best Practice

Baseline Factors Impact Odds For Clinical Remission With Dupilumab In Asthma

March 01, 2025

3 min read

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Key takeaways:

This is a post hoc analysis of the QUEST study.

Baseline factors that positively impacted clinical remission odds on dupilumab included heightened blood eosinophil counts and fractional exhaled nitric oxide.

SAN DIEGO — Researchers found increased odds for clinical remission on dupilumab with high blood eosinophil and fractional exhaled nitric oxide levels in a moderate to severe asthma cohort, according to a poster presented here.

This finding was presented at the 2025 American Academy of Allergy, Asthma and Immunology/World Allergy Organization Joint Congress.

Data were derived from Canonica GW, et al. Abstract 063: Baseline characteristics associated with multicomponent clinical remission following dupilumab treatment in patients with moderate to severe asthma. Presented at: 2025 AAAAI/WAO Joint Congress; Feb. 28-March 3, 2025; San Diego.

In a post hoc analysis of the 52-week phase 3 LIBERTY ASTHMA QUEST study, researchers assessed 1,530 patients with moderate to severe asthma to determine if there are links between clinical remission achievement and three baseline characteristics: blood eosinophil count, fractional exhaled nitric oxide (FeNO) level and pre-bronchodilator FEV1.

"[This is] first evidence of dupilumab reaching 'clinical remission,' an innovative multicriteria tool to evaluate efficacy of a treatment in severe asthma," Giorgio Walter Canonica, FERS, FEAACI, FAAAAI, FACAAI, professor at Humanitas University and senior consultant at the Personalized Medicine Asthma and Allergy Clinic at Humanitas Research Hospital, told Healio.

Giorgio Walter Canonica

"So, not just a single parameter, such as symptoms, but a four-criteria tool: no asthma exacerbations (attacks), no symptoms, no oral corticosteroid (OCS) and stable or improved lung function at 12 months of treatment," he continued. "[This is] a more reliable way to evaluate the effect of a treatment, as in other chronic diseases."

Notably, the poster defined stable/improved lung function as a less than 5% reduction in pre- or post-bronchodilator FEV1 from baseline. Additionally, the no symptoms part of the clinical remission criteria was represented by a 5-item Asthma Control Questionnaire (ACQ-5) score of less than 1.5, which signaled well-controlled asthma.

The study included 1,011 patients who received 200 mg/300 mg add-on dupilumab every 2 weeks and 519 who received placebo.

Within the dupilumab cohort, 387 patients (mean age, 46.2 years; 57.1% women; 81.1% white) met the criteria for clinical remission at week 52, whereas the remaining 624 (mean age, 49 years; 63.6% women; 84.6% white) did not meet the criteria.

In the placebo cohort, 136 patients (mean age, 46.6 years; 61.8% women; 88.2% white) achieved clinical remission at the 52-week mark, and the remaining 383 (mean age, 48.7 years; 65.5% women; 85.4% white) did not.

Between the dupilumab group and the placebo group, a greater proportion of patients receiving dupilumab met the criteria for clinical remission (38.3% vs. 26.2%), according to the abstract.

Following adjustment for several covariates (treatment, age, region, baseline eosinophil strata and baseline ICS dose), researchers found significantly increased odds for clinical remission achievement with dupilumab vs. Placebo among those who had baseline blood eosinophil counts of at least 150 cells/µL (adjusted OR = 2.17; 95% CI, 1.64-2.86; P < .0001), at least 300 cells/µL (aOR = 2.74; 95% CI, 1.92-3.92; P < .0001) and at least 500 cells/µL (aOR = 4.04; 95% CI, 2.45-6.68; P < .0001).

In terms of FeNO levels, the poster reported that patients receiving dupilumab vs. Placebo had significantly greater odds for remission achievement at week 52 when they had heightened FeNO levels at baseline: at least 20 ppb (aOR = 2.35; 95% CI, 1.74-3.16; P < .0001) and at least 50 ppb (aOR = 2.26; 95% CI, 1.38-3.7; P = .0013).

When assessing four different combinations of blood eosinophil counts and FeNO levels (< 150 cells/µL + < 20 ppb; < 150 cells/µL + 20 ppb; 150 cells/µL + < 20 ppb; and 150 cells/µL + 20 ppb), only one reached significance. Researchers observed significantly increased odds for remission achievement with dupilumab vs. Placebo among those with a blood eosinophil count of at least 150 cells/µL plus a FeNO level of at least 20 ppb (aOR = 2.63; 95% CI, 1.88-3.66; P < .0001).

For baseline pre-bronchodilator FEV1, researchers grouped patients as those with 1.75 L or less and those with greater than 1.75 L. Compared with patients in the placebo group, patients in the dupilumab group had significantly elevated odds for remission achievement with a baseline pre-bronchodilator FEV1 of 1.75 L or less (aOR = 1.9; 95% CI, 1.36-2.66; P = .0002). Similarly, the dupilumab group also had significantly heightened odds for this outcome with a baseline pre-bronchodilator FEV1 greater than 1.75 L vs. The placebo group (aOR = 1.61; 95% CI, 1.15-2.24; P = .0051), according to the poster.

"This new approach can be 'translated' in clinical practice as already proposed by our team in Journal of Asthma," Canonica told Healio.

"'Clinical remission' will possibly be 'the' primary outcome of future severe asthma trials, as for other chronic diseases, ie, ulcerative colitis where the FDA [has been] indicating 'clinical remission' as a primary outcome since 2016," Canonica said.

For more information:

Giorgio Walter Canonica, FERS, FEAACI, FAAAAI, FACAAI, can be reached at giorgio_walter.Canonica@hunimed.Eu.

Reference: Sources/DisclosuresCollapse Disclosures: Canonica reports receiving research or clinical trials grants paid to his institution from AstraZeneca, GSK, Menarini and Sanofi Genzyme; and fees for lectures or advisory board participation from AstraZeneca, CellTrion, Chiesi, Faes Farma, Firma, Genentech, GSK, Guidotti-Malesci, HAL Allergy, Innovacaremd, Menarini, Novartis, OM-Pharma, Red Maple, Sanofi-Aventis, Sanofi-Genzyme, Stallergenes-Greer and Uriach Pharma.

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Pulmicort Flexhaler

Pulmicort Flexhaler Generic Name & Formulations General Description

Budesonide (micronized) 90mcg/inh, 180mcg/inh; dry pwd for inhalation.

Pharmacological Class

Steroid.

How Supplied

Flexhaler (90mcg/dose)—1 (60 inh); Flexhaler (180mcg/dose)—1 (120 inh); Respules—30

How Supplied

Pulmicort Flexhaler is available as a dry powder for inhalation containing budesonide in the following 2 strengths: 90 mcg and 180 mcg. Each dosage strength contains 60 or 120 actuations per device. 180 mcg/dose with a target fill weight of 225 mg (range 200-250), and 90 mcg/dose, 60 dose with a target fill weight of 165 mg (range 140-190). 

Storage

Pulmicort Flexhaler should be stored in a dry place at controlled room temperature 20-25°C (68-77°F) with the cover tightly in place. Keep out of the reach of children. 

Generic Availability

Flexhaler (NO); Respules (YES)

Mechanism of Action

Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. The precise mechanism of corticosteroid actions on inflammation in asthma is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have a wide range of inhibitory activities against multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic-mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma.

Pulmicort Flexhaler Indications Indications

Maintenance treatment of asthma as prophylactic therapy. Asthma requiring systemic corticosteroid therapy, to reduce need for systemic corticosteroids.

Pulmicort Flexhaler Dosage and Administration Adult

≥18yrs: Initially 360mcg twice daily; may consider starting at 180mcg twice daily, if appropriate. Max 720mcg twice daily. Rinse mouth after use.

Children

<6yrs: not established. ≥6yrs: Initially 180mcg twice daily; may consider starting at 360mcg twice daily, if appropriate. Max 360mcg twice daily. Rinse mouth after use.

Pulmicort Flexhaler Contraindications Contraindications

Not for primary treatment of acute attack.

Pulmicort Flexhaler Boxed Warnings

Not Applicable

Pulmicort Flexhaler Warnings/Precautions Warnings/Precautions

Maintain regular regimen. Infections. If exposed to chickenpox or measles, consider antiinfective prophylactic therapy. Adrenal insufficiency may occur when transferring patients from systemic corticosteroids to inhaled corticosteroids: see full labeling. Monitor for growth suppression in children. Post-op or during stress: monitor adrenal response. Monitor for hypercorticism and HPA axis suppression (if occur discontinue gradually). Transferring from oral corticosteroids: see full labeling. Pregnancy. Nursing mothers.

Warnings/Precautions

Local Effects

Localized infections with Candida albicans may occur in the mouth and pharynx in some patients.

If these infections develop, patients may require treatment with appropriate local or systemic antifungal therapy and/or discontinuation of treatment.

Rinse mouth after each inhalation. 

Deterioration of Disease and Acute Asthma Episodes

Pulmicort Flexhaler or Respules is not a bronchodilator and is not indicated for the rapid relief of acute bronchospasm or other acute episodes of asthma. 

During treatment, patients should contact their physician immediately if episodes of asthma are not responsive to their usual doses of bronchodilators. Treatment with oral corticosteroids may be needed during such episodes.

Hypersensitivity Reactions Including Anaphylaxis 

Discontinue treatment if hypersensitivity reactions occur, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm.

Immunosuppression

If exposed to chicken pox, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated.

If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated (see the respective package inserts for complete VZIG and IG prescribing information).

May consider treatment with antiviral agents if chicken pox develops.

Use caution in patients with active or quiescent tuberculosis infection of the respiratory tract, untreated systemic fungal, bacterial, viral or parasitic infections; or ocular herpes simplex. 

Transferring Patients from Systemic Corticosteroid Therapy

Use particular care when transferring patients from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency may occur.

The most susceptible patients are those who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent).

A number of months are required for recovery of HPA-axis function after withdrawal from systemic corticosteroids. During this period of HPA-axis suppression, patients exposed to trauma, surgery, infection, or other conditions associated with severe electrolyte loss may exhibit signs and symptoms of adrenal insufficiency.

During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and contact their physicians. These patients should carry a medical identification card.

If oral corticosteroids are required, patients should be weaned slowly from systemic corticosteroid use after transferring to Pulmicort Flexhaler or Respules. For these patients, use Pulmicort Flexhaler or Respules initially with their usual maintenance dose of systemic corticosteroid. Gradually withdraw systemic corticosteroid after approximately 1 week - do not exceed decrements of 25% of the prednisone dose or its equivalent. A slow rate of withdrawal is strongly recommended.

Monitor carefully lung function (FEV1 or AM PEF), beta-agonist use, and asthma symptoms during withdrawal of oral corticosteroids. Observe for signs and symptoms of adrenal insufficiency.

Transfer from systemic corticosteroid therapy to Pulmicort Flexhaler or Respules may unmask allergic or other immunologic conditions previously suppressed by the systemic corticosteroid therapy.

Hypercorticism and Adrenal Suppression  

Use particular care when observing patients post-operatively or during periods of stress for evidence of inadequate adrenal response

Systemic corticosteroid effects may occur, including hypercorticism, and adrenal suppression (including adrenal crisis), particularly when budesonide is administered at higher than recommended doses over prolonged periods of time. Reduce dose of Pulmicort Flexhaler or Respules slowly if these effects occur.

Reduction in Bone Mineral Density

Decreases in bone mineral density (BMD) have been observed with long-term administration of inhaled corticosteroids.

Monitor and treat appropriately in patients with major risk factors for decreased BMD, such as prolonged immobilization, family history of osteoporosis, poor nutrition, or chronic use of drugs that can reduce bone mass (e.G., anticonvulsants and corticosteroids).

Effects on Growth

May cause a reduction in growth velocity when administered to pediatric patients.

Monitor growth routinely if administered to pediatric patients. These systemic effects can be minimized by titrating each patient to their lowest effective dose.

Glaucoma and Cataracts

Monitor closely in patients with a change in vision or with a history of increased  intraocular pressure, glaucoma, and/or cataracts.

Paradoxical Bronchospasm and Upper Airway Symptoms 

Eosinophilic Conditions and Churg-Strauss Syndrome 

In rare cases, may present with systemic eosinophilic conditions.

Health care providers should be alert to eosinophilia, vasculitis rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients.

Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors

Use caution when considering using ketoconazole and other known strong CYP3A4 inhibitors (e.G., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) with Pulmicort Flexhaler or Respules because may potentiate systemic exposure to budesonide. 

Pregnancy Considerations

Risk Summary

Clinical Considerations 

Disease-Associated Maternal and/or Embryo/Fetal risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.  

Labor or Delivery: There are no well-controlled human studies that have investigated the effects of Pulmicort Flexhaler or Respules during labor and delivery.

Nursing Mother Considerations Pediatric Considerations

Safety and effectiveness in asthma patients below 6 years of age have not been established.

Geriatric Considerations

No overall differences in safety were observed between these patients and younger patients.

Hepatic Impairment Considerations

Monitor closely in patients with hepatic disease.

Pulmicort Flexhaler Pharmacokinetics Absorption

Peak steady-state plasma concentrations of budesonide delivered from Pulmicort Flexhaler in adults with asthma (n=39) occurred at approximately 10 minutes post-dose and averaged 0.6 and 1.6 nmol/L at doses of 180 mcg once daily and 360 mcg twice daily, respectively. In asthmatic patients, budesonide showed a linear increase in AUC and Cmax with increasing dose after both a single dose and repeated dosing of inhaled budesonide.  

Distribution

The volume of distribution of budesonide was approximately 3 L/kg. It was 85-90% bound to plasma proteins. Protein binding was constant over the concentration range (1-100 nmol/L) achieved with, and exceeding, recommended doses of Pulmicort Flexhaler. Budesonide showed little or no binding to corticosteroid binding globulin. Budesonide rapidly equilibrated with red blood cells in a concentration independent manner with a blood/plasma ratio of about 0.8.

Elimination

Budesonide is primarily cleared by the liver. Budesonide is excreted in urine and feces in the form of metabolites. In adults, approximately 60% of an intravenous radiolabeled dose was recovered in the urine. No unchanged budesonide was detected in the urine. In asthmatic children 4-6 years of age, the terminal half-life of budesonide after nebulization is 2.3 hours, and the systemic clearance is 0.5 L/min, which is approximately 50% greater than in healthy adults after adjustment for differences in weight. 

Pulmicort Flexhaler Interactions Interactions

Caution with CYP3A4 inhibitors (eg, ketoconazole, itraconazole, atazanavir, ritonavir, indinavir, nefazodone, nelfinavir, saquinavir, clarithromycin, telithromycin).

Pulmicort Flexhaler Adverse Reactions Adverse Reactions

Pulmicort Flexhaler: nasopharyngitis, nasal congestion, pharyngitis, allergic rhinitis, viral upper respiratory tract infection, oral candidiasis, viral gastroenteritis, nausea, otitis media, bronchospasm (rare). Pulmicort Respules: Respiratory or other infection, GI upset, moniliasis, fatigue, cough, dysphonia, rash, epistaxis, hypersensitivity reactions (discontinue if occurs).

Pulmicort Flexhaler Clinical Trials Clinical Trials

The efficacy of Pulmicort Flexhaler was evaluated in two 12-week, double-blind, randomized, parallel-group, placebo-controlled clinical studies (Study 1 and Study 2) which included 1137 patients aged 6 to 80 years with mild to moderate asthma. Both studies had a 2-week placebo treatment run-in period followed by a 12-week randomized treatment period. The primary endpoint was the difference between baseline and the mean of the treatment-period FEV1 (adults) or FEV1% predicted (children).

 

Study 1 (Patients aged ≥18 years)

The study included 621 patients 18 to 80 years of age with mild to moderate asthma previously treated with inhaled corticosteroids.

Patients were randomly assigned to receive either Pulmicort Flexhaler 180mcg, Pulmicort Turbuhaler 200mcg, or placebo administered as 1 inhalation once daily or 2 inhalations twice daily.

Results showed that patients treated with Pulmicort Flexhaler 180mcg (2 inhalations twice daily) achieved a mean change from baseline in FEV1 of 0.28 liters compared with 0.10 liters in the placebo arm (P <.001).

Patients treated with Pulmicort Flexhaler also met secondary endpoints of morning and evening peak expiratory flow rate, daytime asthma symptom severity, nighttime asthma symptom severity, and daily rescue medication use compared with placebo (P <.001).

 

Study 2 (Patients aged 6 to 17 years)

The study included 516 patients 6 to 17 years of age and older with mild to moderate asthme previously treated with inhaled corticosteroids.

Patients were randomly assigned to receive either Pulmicort Flexhaler 90mcg 2 inhalations twice daily or 4 inhalations twice daily; or Pulmicort Turbuhaler 200mcg 1 inhalation once daily or 2 inhalations twice daily; or placebo.

Results showed that patients treated with Pulmicort Flexhaler 90mcg 4 inhalations twice daily achieved a mean change from baseline in % predicted FEV1 of 5.6 compared with 0.2 in the placebo arm (P <.001).

Patients treated with Pulmicort Flexhaler also met secondary endpoints of morning and evening PEF compared with placebo (P <.001).

Pulmicort Flexhaler Note

Not Applicable

Pulmicort Flexhaler Patient Counseling Patient Counseling

Oral Candidiasis

Advise patients that localized infections with Candida albicans occurred in the mouth and pharynx in some patients.

Treat with appropriate local or systemic (i.E., oral) antifungal therapy while still continuing therapy with Pulmicort Flexhaler or Respules if oropharyngeal candidiasis develops; at times, may need to temporarily interrupt Pulmicort Flexhaler or Respules under close medical supervision.

Advise patients to rinse their mouth after inhalation.

Not for Acute Symptoms

Do not use to relieve acute asthma symptoms, and do not use extra doses for that purpose.

Use inhaled, short-acting beta2-agonist (i.E., albuterol) to treat acute symptoms.

Notify health care professional immediately if patients experience:

Decreasing effectiveness of inhaled, short-acting beta2- agonists 

Need for more inhalations than usual of inhaled, short-acting beta2-agonists

Significant decrease in lung function as outlined by the physician

Do not stop therapy without physician/provider guidance.

Hypersensitivity Including Anaphylaxis

Discontinue if hypersensitivity reactions occur, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm.

Immunosuppression

 Hypercorticism and Adrenal Suppression 

Advise patients that treatment may cause systemic corticosteroid effects of hypercorticism and adrenal suppression.

Slowly taper patients form systemic corticosteroids if transferring to Pulmicort Flexhaler or Respules.

Reduction in Bone Mineral Density

Reduced Growth Velocity 

Ocular Effects

Use Daily 

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