Management of Acute Respiratory Tract Illness: Case Study and Evaluation

Case History

64yo female presented with her son. Unwell for the last 2/7 with intermittent fevers, dry cough, body aches, shortness of breath (SOB) with wheezing associated and generalised weakness. No chest pain or palpitations.

Past medical history:

1. Type 2 Diabetes Mellitus (T2DM)  with diabetic nephropathy since 2008 – on insulin
2. Hypertensive disease
3. Gout
4. Obesity

Allergies: No known drug allergies (NKDA)

Medical Warnings: Avoid NSAIDS and Metformin

Social history: Non-smoker and Non – drinker.  She is living with son and daughter- in-law. Independent with ADLs (Activities of daily living).

Medications:

1. T. Amlodipine 10mg po daily
2. T Cilazapril 2.5mg po daily
3. T Allopurinol 300mg po daily
4. Inj Lantus 45units sc nocte
5. T Panadol 1000mg po QID as required

O/E: Temp 38.8, PR-112/min, BP-126/70mmHg, Sats-95% OA, PF-100 (poor technique)

Comfortable, not in any respiratory distress

Oropharynx: Erythematous, no purulent discharge noted

Chest: reduced air entry with coarse breath sounds

Heart: HS dual, no murmur

MSK: No pedal oedema

Imp: Chest infection

Plan:

1. T Amoxycillin 500mg po TDS for 7 days
2. T Prednisone 40mg po daily for 5 days
3. T Panadol 500mg 2 X tabs po Q4H-Q6Hrly PRN
4. S codeine phosphate Linctus 15mg/5ml 10ml po nocte/PRN
5. Advised to return for influenza vaccination once recovered from this illness.

Research Questions:

Is there a role for corticosteroids (oral or inhaled) alone or in adjuvant with other treatments in community acquired chest infection?

Background:

Acute lower respiratory tract infection in the community is generally not managed well. Oral corticosteroids and antibiotics are often used non – discretionally. It is well known that oral corticosteroids has beneficial role in asthma and chronic obstructive pulmonary exacerbation management. It is assumed that using corticosteroid alone or in conjunction with antibiotic is the better choice to have good outcome.  The following research attempts to deduce whether oral corticosteroids are effective in reducing hospital admissions or duration of illness in non-asthmatics or patients with bronchitis (both adults and children) and its role in upper respiratory tract infection management.

Management of acute respiratory tract illness: NICE guidelines.

The Best Practice Advocacy Centre New Zealand (bpacnz) identified the importance of National Institute of Clinical Excellence (NICE) guidelines in management of respiratory tract infections. With approval from NICE, bpacnz has produced a revised guideline to manage acute respiratory tract infections.

An immediate antibiotic treatment along with further investigation should be offered in the following category of patients:

–          Those who are systemically unwell and have signs and symptoms indicative of a critical illness and or with complications (e.g. pneumonia)

–          High risk patients with a background of chronic medical problems which can lead to serious complications.

–          Patients with acute cough/acute bronchitis with a record of poor / non-compliance to attend clinic in the situation where their clinical signs and symptoms get worse.  Patient who are below 2 years and from low socioeconomic status areas, those with poor housing including overcrowding and those with other cultural barriers to healthcare.

–          Elderly patients >65 years with acute cough and two or more of the following from criteria below, or those who are over and above 80 years with acute cough and one or more of the following from criteria below:

• Past history of admission to the hospital in last year
• Chronic medical conditions like Type 1 or Type 2 Diabetes mellitus
• History of Cardiac failure
• Regularly using oral steroids

“No antibiotic prescribing strategy and the delayed antibiotic prescribing strategy should not be considered for the above patients”¹.

Current NICE guidelines do not include the use of oral or inhaled corticosteroids in the management of acute respiratory illness.

In contrast to the above, management of community acquired chest infection (CAP) according to  Auckland regional pathway encompasses the use oral antibiotic based on the eligibility criteria which includes diagnosis of CAP based on presence of cough plus lower respiratory tract illness symptoms such as chills, sweats, breathlessness, pleuritic chest pain, fatigue, weakness and body aches. Focal signs include chest crackles, harsh breath sounds and at least one systemic feature such as temperature > 38 degrees Celcius, sweating, and shivering with a respiratory rate (RR) > 24 per minute and heart rate > 100 per minute.

Once the diagnosis of CAP is certain, severity should be assessed through the CURB- 65 score (Confusion, respiratory rate (RR>30), urea and blood pressure either systolic pressure < 90 mmHg or diastolic blood pressure <60 mmHg). Each component gets once point and based on the score, CAP is categorised as mild with a score of zero, moderate with a score of one and moderate to severe with a score between two to four.

Patients with CURB-65 score zero or one would be suitable candidates for treatment in the community based on their ability to access healthcare, reliably take medication and have adequate social support. Patients can be monitored at home by a care-giver.  If complications arise such as empyema, lung abscess and septicaemia then they have to get admitted to the hospital.

Patients with CURB- 65 score zero or one is managed in the community with oral antibiotics. First line treatment are amoxicillin, doxycycline, roxithromycin and augmentin for those with chronic obstructive pulmonary disease (COPD)².  COPD is also managed with bronchodilators to address air flow limitation and analgesics for pleuritic chest pain. Smoking cessation is recommended;currently there is no role for oral or inhaled corticosteroids for the management of community acquired pneumonia.

Both NICE guidelines and Auckland regional pathways does not encourage the use of antibiotics early in the disease or steroids in any form (oral or inhaled or parental) as it has not proven to be beneficial.

The following two studies favours use of antibiotics in certain conditions only:

A randomised controlled trial (RCT) paper published in JAMA 2005, involving 807 patients attending their family doctors with the simple acute lower respiratory tract infections were categorised into three groups : immediate antibiotic (n=262), a delayed antibiotic prescription (n=272) and no offer of antibiotics (n=273) were prescribed and outcome measured on symptom duration and severity.  Final conclusion was that not to prescribe antibiotics immediately or later for the simple acute respiratory tract illness is welcomed as due to minimal symptom improvement.³

Article on diagnosis and management of acute bronchitis published in American family physician in 2002 did mention that acute bronchitis is one of the top 10 reasons why people see their physicians for. Since in most cases the cause for bronchitis is viral, it can be treated conservatively with the anti-tussives, bronchodilators or pro-tussives rather than antibiotics which most of the physicians have a habit of prescribing. Antibiotics are ineffective in acute bronchitis and are largely unnecessary and lead to increased risk of antibiotic resistance⁴.

So far it is evident that antibiotics have only few benefits in acute respiratory tract illness based on individual factors. It would be interesting to know whether oral prednisolone has a role in management of acute lower respiratory tract illness (LRTI). A randomised controlled trial published in the Journal of Acute American Medicine (JAMA) looked at the “effects of oral prednisolone on symptom duration and severity in non-asthmatic adults with acute LRTI”⁵ . This study was performed on patients in the community with participants from 54 family centres in England and with eligibility criteria that encompassed no use of any bronchodilators in the last 5 years. Patients with COPD were excluded. Eligible patients (401) were treated with 40mg of Prednisolone and 202 with placebo (no prednisolone) for duration of 5 days. Primary outcomes measured were the duration of cough and mean severity of symptoms.  Secondary outcomes measured were “duration and severity of symptoms, duration of abnormal peak flow, antibiotic use and adverse effects”⁵.  The conclusion was that the use of oral corticosteroids does not reduce symptom duration or severity in non-asthmatic patient with acute respiratory tract illness⁵.

In contrary to the above, the systematic review and meta-analysis on corticosteroid therapy for patients hospitalised with community acquired pneumonia published in ‘annals’ of internal medicine on 2015 concluded that corticosteroids have a beneficial role in hospitalised patients with community acquired pneumonia in reducing mortality by approximately 3% and need for mechanical ventilation by 5% and reduced hospital stay by approximately 1 day.⁶  This is quite significant in the hospitalized patient.

A systematic review published in Cochrane database in 2012 assessed the usefulness of corticosteroids as an adjunct as well as a standalone treatment of sore throat in adults and children.  Eight trials involving 743 participants (369 children and 374 adults) were included in this research. Both placebo and corticosteroid groups were given oral antibiotics in all of trials. There were no trials that assessed the use of corticosteroids as a standalone treatment for sore throat. In addition to any effect of antibiotics and analgesia, corticosteroids increased the likelihood of complete resolution of pain at 24 hours by more than 3 times (risk ratio (RR) 3.2, 95% confidence interval (CI) 2.0 to 5.1, P < 0.001, I(2) statistic 44%) and at 48 hours by 1.7 times”⁷. This concluded that the use corticosteroid in addition to antibiotic and analgesics has increased the chances of pain reduction in patients with sore throat⁷.

A further literature search was conducted to look for evidence of benefits / role of corticosteroids in the treatment of acute respiratory tract illness both as a sole therapy and as adjunct therapy to antibiotics.

It was evidential that oral steroids have a beneficial role in treatment of asthma during acute exacerbations through its anti-inflammatory properties. It relieves the bronchospasm and alleviates shortness of breath and wheezing. It is also proven to be beneficial in acute exacerbation of chronic obstructive pulmonary disease (COPD).  Acute exacerbation of COPD is a common cause for hospitalization and mortality in older population groups and it causes reduction in lung function, physical incapacity and reduced quality of life.

A systematic review published in Cochrane database in 2014 confirms beneficial role of oral corticosteroids in the acute exacerbation of chronic obstructive pulmonary disease. The goal of the study was to differentiate the effect of oral or parental corticosteroids and its efficacy. “Sixteen studies (n = 1787) met inclusion criteria for the comparison systemic corticosteroid versus placebo and 13 studies contributed data (n = 1620). Four studies (n = 298) met inclusion criteria for the comparison oral corticosteroid versus parenteral corticosteroid and three studies contributed data (n = 239)”⁸.

In conclusion, the review concluded that there is high-quality evidence to support treatment of exacerbations of COPD with the systemic corticosteroids by the oral or parental route in reducing the likelihood of treatment failure and relapse by one month, earlier improvement in lung function onland improvement of symptoms. However, no evidence of benefit for parental treatment Vs oral treatment with corticosteroid on treatment failure, relapse or mortality was noted. There is an increase in adverse drug effects with corticosteroid treatment, which is greater with parenteral administration compared with oral treatment.⁸

A systematic review on corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease published in a 2002 JAMA internal medicine studied the usefulness of systemic corticosteroids in acute exacerbation of COPD management. They also assessed the adverse effects of corticosteroid, treatment failure rate and length of hospital stay. Spirometric differences in treatment groups versus placebo groups were used as measurable outcomes.  With the steroids administration 5 out of 8 studies showed significant improvement in forced expiratory volume (FEV1) by more than 20%. Clinical improvements were noticed in 2 out 8 studies⁹. Final verdict was short course of systemic corticosteroids in the acute exacerbation of COPD showed both clinical and spiromteric improvements⁹.

Another publication in the international journal of chronic obstructive pulmonary disease in 2014 looked upon the role of corticosteroids in treatment acute exacerbation of COPD. “In comparison to placebo, systemic corticosteroids improve airflow; decrease the rate of treatment failure and risk of relapse. Systemic corticosteroids also improve symptoms and decrease the length of hospital stay.  Therefore, corticosteroids are recommended by all major guidelines in the treatment of acute exacerbation of chronic obstructive pulmonary disease. Existing literature suggests that low-dose oral corticosteroids are as efficacious as high-dose, minimizing adverse effects”^10.

A Publication in a BMJ on 26th may 1984 discusses about the use of steroids in chronic bronchitis. It was noted that patients with acute limitation of air flow caused by inflammation and bronchoconstriction during acute exacerbation respond well to the course of steroids rather than those with chronic air flow limitation caused by emphysema. This is probably due to lack of support from the surrounding lung tissues leading to air flow narrowing, collapsing and distortion of air way¹¹.

A 40% increase in forced expiratory volume (FEV1) was noted in those who were treated with steroids along with antibiotic and bronchodilators during acute exacerbation after 72 hrs (12 of 22 patients) when compared to the placebo group (3 out of 21). It was found that that most of the responders showed significant changes by 8 days with oral prednisolone 30-40mg on board and those with inhaled steroids (800 microgram a day) showed further improvement in FEV1¹¹.

Another article published in the American family physician in 2010 on management of COPD exacerbations suggests that higher mortality is associated with exacerbation of chronic obstructive pulmonary disease. RCTs have proven that multiple interventions are effective in the acute exacerbation of COPD. Increasing the dose of inhaled corticosteroids and addition of oral corticosteroids has proven beneficial in patients with purulent phlegm. Addition of antibiotic helps in decreasing the treatment failure and also mortality in moderately severe illness. This article encourages physicians to prescribe antibiotic especially if they are producing purulent sputum and in those who are not adequately responding to the combination of inhaled and oral corticosteroids. Choice of antibiotic is based on patient history of antibiotic use and its resistance^12.

All the studies above confirmed that the systemic corticosteroids are efficacious and should be considered a standard of care for patients experiencing an acute exacerbation of chronic obstructive pulmonary disease. Therefore systemic corticosteroids should be administered to all patients experiencing acute exacerbation that is severe enough to seek emergent medical care. The lowest effective dose and shortest duration of therapy should be considered in order to minimise the adverse effects.^8,9,10,11,12

A systematic review published in Family practice in 2013 on corticosteroids for acute and sub-acute cough following a respiratory tract infection was based on use of inhaled corticosteroids for management of acute and sub-acute cough in respiratory tract infection. They reviewed seven electronic database and five ongoing trials among family practices in United Kingdom (UK). They found that the results were mixed, two showing equivalence report and two showed benefits in cough score (p = 0.012) and mean cough frequency (p=0.047). One trial reported additional benefit in the non-smokers.  Adverse effects were rarely identified and no record on patient satisfaction or subsequent development of asthma was available ¹³.

Overall, there is an inadequate evidence for the use of inhaled corticosteroids in setting of cough in acute respiratory tract illness. However, some noted benefits warrant more high quality and powered studies¹³.

An overview of review published in 2014 reviewed the Cochrane Database in February 2013 for systematic reviews comparing systemic corticosteroids with placebo for children between the age group of 0-18 with acute asthma, preschool wheezing, bronchiolitis, croup, pharyngitis/tonsillitis or pneumonia.  It was found that systemic corticosteroids in otherwise healthy children are safe to prescribe for the management of acute respiratory conditions (i.e. infections or asthma exacerbations) with minimal concern about short‐term adverse effects¹⁴.

Benefits from the use of oral, inhaled and parental corticosteroids have been reviewed in the above literature. A paper published in the Journal of chronic obstructive pulmonary disease in 2017, assessed the serious adverse effects with the use of inhaled or oral corticosteroids in COPD. They found that the use of corticosteroids is associated with increased risk of infection, especially pneumonia. Sepsis risk has been little studied in COPD with corticosteroids use. They included 163,514 patients including 1704 who were hospitalized or died with sepsis during follow-up (incidence rate 1.94 per 1000 per year). The relative risk (RR) of sepsis was 0.98 with 95% CI 0.84-1.14 for those with the use of inhaled corticosteroids. In comparison, a 66% increase in the risk of sepsis was associated with oral corticosteroid use (RR 1.66; 95% CI: 1.35-2.05)¹⁵. Risk remains high for around 5 months after the use of oral corticosteroid. The risk of sepsis as noted to be high with oral corticosteroids then with inhaled corticosteroids COPD treated patients¹⁵.

Conclusions:

It is evident that use of corticosteroids particularly via oral route in the acute respiratory tract infection has not been researched enough in non-asthmatic patients. It is evident that use of oral corticosteroids in children with certain acute respiratory conditions and as well as in patients with chronic obstructive pulmonary disease and asthma during its exacerbation has a beneficial role.

The use of oral corticosteroids in combination with antibiotics is superior in the treatment of throat infection when compared to antibiotics or oral steroids alone. Slight increase in risk of sepsis is noted however among chronic obstructive pulmonary disease patient during exacerbations from oral corticosteroid use.

One has to be very vigilant and thoughtful before prescribing oral corticosteroids while treating respiratory tract infections as we know that there is no much benefit and in turn it adds on to the cost of the healthcare. Patients with background history of asthma and chronic obstructive pulmonary disease would benefit with oral corticosteroids in the event of infective exacerbation of their conditions. Likewise steroids can be used wisely for children given the benefits of restraining those patients from getting admitted to hospital.

In reflection to the case above, management was appropriate given that the patient is elderly with probable underlying bronchitis which needs further exploration. Once patient’s condition has improved, a referral to spirometry would help to diagnose whether this patient has bronchitis or has underlying asthma/chronic obstructive pulmonary disease. Treatment of underlying condition would benefit patient from getting frequent exacerbations and may help prevent hospital admissions.

Recommendations:

• Oral or inhaled corticosteroids alone are not recommended for non-asthmatic patients during acute respiratory tract illness.
• The lowest effective dose and shortest duration of corticosteroid therapy should be considered in order to minimise the adverse effects in the event of acute exacerbations of asthma and chronic obstructive pulmonary disease in adults.
• Systemic corticosteroids in otherwise healthy children are safe to be prescribed for management of acute respiratory conditions (i.e. infections or asthma exacerbations) with minimal concern about short‐term adverse effects.
• No offer or delayed offer of the antibiotics for the uncomplicated acute respiratory tract illness is acceptable as there is little symptom resolution only.
• The use of corticosteroids in addition to antibiotics and analgesia has increased chances of resolution and improvement of pain only in patient with sore throat. Further research is required for use of steroids alone for upper respiratory tract management.
• There is an inadequate evidence for the use of inhaled corticosteroids in the setting of cough in acute respiratory tract illness. Further research is required.

References:

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