Obstructive lung disease – asthma and COPD

Asthma.

Assessing severity in an acute attack:

• Measure and document the peak flow (normally >450 l/min in a young woman, and > 600 l/min in a young man.)
• Document the pulse rate (beware if >100 bpm), the blood pressure and the magnitude of the pulsus paradoxus (beware if >20 mmHg, or if it was high and is now decreasing without other signs that the patient is improving – this may indicate muscle fatigue.)
• Can the patient talk in full sentences?
• Does the patient appear to be ‘tiring’?
• Is the P_aO₂ < 8kPa on 40% oxygen?
• Is the PaCO₂ above the normal range, or rising into the normal range if an earlier value was low?
• Is the chest relatively ‘silent’? (i.e. air entry appears worse than it was earlier).

Managing an acute attack

• Place on 40% oxygen and reassure the patient while preparing the first nebuliser.
• Nebulise with 1 ml (5 mg) of salbutamol in 4 ml saline at 6 l/min flow rate. Repeating this when the nebuliser is finished after 15 to 20 minutes, effectively gives ‘continuous’ nebulisation of salbutamol at a rate of 15mg per hour.
• Once the patient is settling (peak flow > 60% of predicted) reduce rate to 4 hourly.
• Unless the patient responds rapidly, give hydrocortisone 200 mg IVI slowly once, and continue with prednisone 40 mg daily for 7 days.
• Do peak flow rates before and after nebulisation, and document the results.
• If no nebuliser available use a large volume spacer: 10 puffs from a salbutamol metered dose inhaler into the spacer.¹
• If not clearly settling, either continue to observe till settled or, if worsening, consider transfer to a high care area in your hospital, and be prepared to intubate.
• Patients commonly settle in casualty and are then sent to a ward where nebs and monitoring is suboptimal. Always physically check on such patients after an hour or so, and personally tell nursing staff the importance of ongoing nebs and the need to let you know if the patient does not continue to improve.

Other considerations if not settling:

• Not asthma (cardiac failure?)
• Undiagnosed pneumothorax.
• Nebulisation not actually being given, or being given incorrectly.
• Associated chest infection?
• Consider intravenous magnesium sulphate 2 g over 20 minutes (4 ml of 50% solution containing 500 mg per ml), diluted in 200 ml 5% DW or normal saline and infused over 20 minutes (remember magnesium sulphate and hydrocortisone should not be given together – precipitation.) The evidence of efficacy on patient-relevant and clinically important endpoints is weak.
• In very ill non-responding patients, theophylline IV is recommended, again without convincing evidence of efficacy – the usual dose is a load of 5 mg/kg/hour (assuming patient not already on the agent) followed by an infusion of 0.5 mg/kg/hour.
• The combination of corticosteroids, salbutamol, and then theophylline on top results in the use of three agents known to lower the serum [K⁺], monitor it regularly in the acute phase.

Ventilation in acute asthma

Beware of extra-thoracic obstruction masquerading as asthma – such patients may prove catastrophically difficult to intubate. Think of this in persons with recent neck trauma or difficulty swallowing, or no background of chronic wheeze. In this situation the wheeze may be predominantly inspiratory.

The presence of a physical irritant (the tube) in an already compromised system may worsen bronchospasm – use local anaesthetic for the upper airway, and if concerned, put a little down the tube as well.

Don’t sedate the patient with morphine as all opiates can worsen asthma in certain individuals. If needed, you can put 100 mg (10 ampules) of diazepam in 1 litre (1000 ml) of 5% dextrose water and run it at 50-100 ml/hr (i.e. 5-10 mg/hr).

Ventilator settings

• Do not use any PEEP.
• The insp:exp ratio should be 1:2.5 or greater
• Use lowish tidal volumes – e.g. 400 to 500 ml for an average adult.
• Keep inspiratory flows low to avoid barotrauma and pneumothorax development – frequently one needs very high pressures to ventilate these patients at all, so don’t exacerbate the situation by blowing the air in faster than necessary. If ‘sigh’ is available this should also be OFF.
• Don’t be shy to use high FiO2 in the initial phase.
• Don’t forget to continue the hydrocortisone (100 mg 6 hourly)² and ensure that the patient continues to get regular nebulisation on the ventilator
• Check the [K+] early as the combination of salbutamol, hydrocortisone (and sometimes theophylline) tends to cause marked hypokalaemia.

Perspective – nebulisation.

A study from a university hospital in Singapore³ found that only 21.5% of prescriptions for nebulisation were complete. The script should state:

• drug dose,
• volume of diluent (if any),
• flow rate of driving gas
• frequency of nebulisation.

One of the reasons for poor prescribing of nebulisers may have to do with the lack of clarity about the optimum way to give them. The nihilist’s view is that it probably doesn’t matter that much, but in the context of patients who are quite desperately sick, it seems to make sense to try to get things right.

Two key problems have to do with the dose of salbutamol (UK recommendations are different to those of US recommendations) and whether or not to dilute. (The package inserts recommend this for ipratropium but not for salbutamol in South Africa; the UK package insert for salbutamol says either diluted or undiluted is acceptable.)

One study⁴ showed that only about 20% of a salbutamol nebuliser solution of 2.5 mg placed in a nebuliser actually gets as far as the mouthpiece in a respirable form (1-5 micrometres particle size). While the volume of diluent (more is better), and the driving gas flow rate influence the delivered respirable mass, the brand of nebuliser also made a difference.

A paediatric single-blinded study⁵ which randomised 50 patients to diluted or undiluted salbutamol appeared to demonstrate that the two were equivalent in terms of FEV1 response, and that the undiluted nebuliser took only six minutes versus three 10 minute nebs for the diluted version. The total dose of salbutamol prescribed was however twice as much in the undiluted group, so the validity of this study is somewhat dubious.

Comment: The issue is unresolved, but from a pragmatic perspective giving serial diluted nebulisers with salbutamol 1ml (5 mg) diluted with 4 ml saline approximates to the use of ‘continuous nebulisation, and allows the easy substitution of 2 ml of the saline with ipratropium if required (1ml salbutamol, 2 ml ipratropium, 2 ml saline). This avoids the need for different dilution protocols for nursing staff, and doesn’t waste any more oxygen, because patients will in any case be on a 40% oxygen mask between nebs when initially seen.

Deciding when it is safe to discharge an asthmatic

When there is a lot of bed pressure, there is often a temptation to discharge asthmatics a bit early; they tend to come back the next night. Look for:

• Pulse rate less than 100 beats per minute.
• Able to walk to the toilet unassisted.
• No early morning dipping on peak flow chart.
• Little variability of peak flow – values before and after nebs are very similar.
• Peak flow is greater than 80% of normal for age and gender.
• Patient agrees that he or she is ready to go home.

Follow-up after an acute attack

All patients admitted for an acute attack should be discharged on oral prednisone in a dose of about 30 mg/day, which can be stopped after a week to ten days (tailing doses are not necessary). If there are serious concerns about adherence, intramuscular methylprednisolone depot is a feasible alternative,⁶ but the dose needed is higher than commonly used – e.g. 160 mg IMI stat. When seen in outpatients after an acute attack, check the following:

• Does the patient understand what asthma is and what to expect from caregivers in terms of regular peak flow monitoring?
• Does the patient know the difference between preventers (steroids) and relievers (beta-agonists)?
• Does the patient know his or her target peak flow?
• Does the patient know to stay on inhaled corticosteroids for 6 to 12 months?

Determining predicted peak flow is easiest using an online calculator such as this one.

Long-term management of asthma

There is still a belief that asthma can be managed with beta-2 stimulants alone. The only situation where this might be true is ‘pure’ exercise induced asthma (EIA). EIA is a diagnosis of exclusion – take a careful history to elicit asthma symptoms at times other than while exercising, based on the premise that EIA is perhaps only manifesting in the exercise space in an otherwise relatively mild (but still symptomatic if you look) asthmatic.

Severe asthma is not just asthma causing hospital admission – any patient who is waking up at night because of cough or wheeze, even if only once a week, warrants prompt treatment.

The first-line therapy is an inhaled corticosteroid such as beclomethasone, 200 mcg twice daily. This can be increased to 400 mcg twice daily if inadequate response after 3 months. If still inadequate response, replace with salmeterol/fluticasone 25/125 mcg two puffs twice daily.

Personally check inhaler technique.

All asthmatics warrant a peak flow measurement at every visit. (You wouldn’t try to treat hypertension without checking the blood pressure.) The addition of oral theophylline is no longer considered appropriate for the majority of patients.

Exercise induced asthma and inhaled corticosteroids

If standard short acting beta-2 stimulants are inadequate to achieve control in EIA, the addition of a combination LABA and corticosteroid has some evidence for increased efficacy, and may be worth attempting. Beware that you aren’t in fact dealing with an asthmatic with more extensive symptoms just manifesting predominantly on exercise, and ensure that PF is monitored outside the exercise situation as well.⁷

Perspectives – asthma

There are a considerable number of high-quality meta-analyses in this area:

Giving corticosteroids IV within one hour of presentation to casualty reduces need for hospital admission⁸ (OR 0.4, 95% CI 0.21-0.78, NNT 8.) In children, oral steroids worked as well; evidence for this in adults is not available. Inhaled corticosteroids achieve a similar effect size⁹ (OR 0.33, 95% CI 0.17 – 0.64), but this was not significant if the patient also received systemic steroids, so if you are going to give the IV hydrocortisone anyway, there’s not much to be gained by adding inhaled corticosteroids.

In chronic asthma, another meta-analysis¹⁰) showed that inhaled beclomethasone improved FEV1 by an average of 340 ml and reduced the need for rescue beta agonists by an average of 1.75 puffs per day (95% CI 1.4-2.4 puffs/d) Higher doses of inhaled corticosteroids were found to be only marginally better than lower doses, and did not lead to a significant reduction in the use of systemic corticosteroids in patients already on these agents.

Chronic Obstructive Pulmonary Disease (COPD)

Take a history of base-line effort tolerance. This is the most reliable indicator for differentiating between asthma and COPD. Although the two conditions seem very similar because they both present acutely with wheeze and hyperinflation, there are important differences. Asthma is essentially a fully reversible condition where the goal of therapy should be to return the patient to a completely normal life-style. COPD is a permanent, slowly progressive disability where patents can be returned to base line after acute exacerbations, but have permanently limited effort tolerance.

Besides the well-known ‘classic’ features of COPD, a combination of all four features of a self-reported history of COPD, a history of smoking more than 40 pack years, age more than 44, and a laryngeal height of less than 4 cm had LR+ of 220 in distinguishing COPD patients from ‘normal’.¹¹ (The laryngeal height is the distance from the top of the thyroid cartilage to the suprasternal notch.)

As usual, the well-taught signs don’t always perform that well in practice: a study ¹² looking at GP’s ability to correctly diagnose COPD using various features found the usual prevalence-dependent issues of disappointing sensitivity, but highlighted the importance of taking a smoking history and percussing the chest:

Prognostication in COPD

The table gives a mortality score associated with age and risk factors in patients with an acute presentation.

¹³

Management of an acute exacerbation of COPD

Give nebulised salbutamol 1 ml (5 mg) diluted in 4 ml of saline 4 hourly. Increase to 2 hourly if necessary and tolerated.

If there is evidence of infection (fever, purulent sputum, pleuritic chest pain) give amoxicillin/clavulanate 875/125 mg 12 hourly for 5 days, recognising that some infections may be viral. If the patient is very ill, consider intravenous ceftriaxone.

It is very tempting to put all distressed patients on oxygen. Remember that some patients with COPD, particularly those who are deeply cyanosed and oedematous and have associated cor pulmonale, are running on a hypoxic drive, and starting 40% oxygen may cause them to stop breathing altogether. If you are planning to use oxygen in that situation, start with 28%, and watch the patient for signs of drowsiness or marked respiratory slowing. Aim for so-called ‘safe sats’, between 88% and 92% – values higher than that increase the risk of hypercarbia without conferring any advantage on the patient. An alternative, if available is to do two blood gases – one initially, and one after 20-30 minutes . If the CO2 rises by more than 1 kPa, then consider there is high risk of worsening hypercarbia and reduce the provided oxygen concentration.

• Steroids can be given in a short course – e.g. prednisone 40 mg/day for 5 days ¹⁴ – but beware of giving steroids long term in patients with background post-tuberculous lung disease.
• Consider co-existing cardiac failure, and avoid NSAIDS and opiates.
• Do not forget to advise about stopping smoking!

Timing of discharge in COPD

With current bed constraints, it is also useful to consider when to switch to oral treatment and discharge. Although some guidelines on this have been published the key principle seems to be to observe the ‘glide-path’ of the patient and his or her disease. If the temperature and respiratory rate is falling, and progression to recovery is steady, then it is reasonable to change to oral therapy and discharge a day later if there has been no deterioration. This day’s wait is conservative and depends on local circumstances and the patient’s ability to return if not settling. Explain about returning if deterioration should occur – premature discharge may be seen by the patient (and the patient’s family) as evidence of poor care, warranting costly and unnecessary presentation at another hospital.

Management of stable COPD

The GOLD classification is intended for stable patients but newer versions may not necessarily improve prognostic accuracy.¹⁵ Whichever version of whatever prognostic process is used, worsening age, exercise limitation, and lung function testing correlate with worse prognosis, as expected; it is the magnitude of the mortality effect that is worth noting.

Managment

Advising patients to stop smoking is cheap and highly beneficial if the advice is taken – it is always worth a try.

If there is a degree of reversibility, use salbutamol 200 mcg inhaler 3 x/d; if ineffective, and in consultation with a specialist, substitute with formoterol inhaler 12 mcg 2x/d.

There is a case to be made for a salmeterol/fluticasone 25/125 mcg inhaler (2 puffs 2x/d) (or formoterol/beclomethasone) if patients are experiencing more than two exacerbations per year. Adding low dose oral theophylline to patients already on inhaled corticosteroids does not appear to be helpful and may cause harm.

Perspective – therapies in COPD.

Stopping smoking in COPD patients

In resource-constrained environments, chronic lung disease secondary to pneumoconioses and incompletely treated or late-treated tuberculosis plays an important part in the aetiology of COPD. However smoking is becoming an increasing problem.

In the US, half of all people who have ever smoked have managed to quit.²⁹ Although counselling about smoking is not particularly effective (20% cessation rate at 6 months) it is cost-effective simply because the intervention is so easy. Talk is cheap! Try the five As³⁰ :

Activity	Comment
Ask about use	It takes a couple of seconds each visit.
Advise to quit	Don’t go off on a long diatribe, but state clearly that its worthwhile and why.
Assess willingness	Just ask if willing to stop.
Assist	Extra counselling. Set a quit date.
Arrange follow-up	Make a date to see how it’s going.

Smoking cessation results in a 50% reduction in rate of decline of lung function but only about 35% of patients manage to stop even for one year, and at five years up to 78% of a cohort were smoking again, even with support from counselling, gum and patches.³¹ A randomised trial³² of a 10-week smoking cessation programme in 5887 individuals with mild airflow limitation also demonstrated a 22% quit rate at five years (versus 5% in controls), and followed the groups for up to 14.5 years. All cause mortality was 8.8/1000 person-years in the intervention group versus 10.4/1000 in the control group (a modest but statistically significant difference).

Vaccination for COPD patients

Influenza vaccination is probably of value, although not always easy to access through the public health system. In terms of cost-effectiveness, it is probably a very reasonable option for this specific group of patients.³³ Owing to its cost, pneumococcal vaccination is more controversial. (Its cost is an order of magnitude higher than the cost of influenza vaccination, which is about the same as the cost of a FBC.)

Oxygen for COPD patients on the way to hospital

An observational study³⁴ of COPD patients given supplemental oxygen by paramedics found that those given <28% had mean pH of 7.4, PaCO₂ 6.1, and 21% complicated admissions; those given >28% had pH of 7.2, PaCO₂ 11.7, and 73% complicated admissions.

Other wheezes.

Consider:

• Pulmonary oedema due to cardiac failure (Apex, S3, ECG, CXR).
• Pulmonary embolism(Calf swelling, abrupt onset)
• Loeffler’s syndrome (pregnant women with pica – eosinophil count)
• Stridor (the wheeze is inspiratory rather than expiratory, although it can be both) – this may be due to intrinsic issues such as a foreign body, or extrinsic compression.

---

1. Hendeles L, Hatton RC, Coons TJ, et al. Automatic replacement of albuterol nebuliser therapy by metered-dose inhaler and valved holding chamber. Am J Health-Syst Pharm. 2005;62:1053-61 ↩

2. Manser R, Reid D, Abramson M. Corticosteroids for acute severe asthma in hospitalised patients. (Cochrane review). In: The Cochrane Library, Issue 1, 2000. Oxford: Update Software ↩

3. Khoo SM, Lim TK. Prescribing and administration of nebulized bronchodilators: a prospective audit in a university hospital. Respirology. 2003;8:205-7 ↩

4. Hess D, Fisher D, Williams P, et al. Medication nebulizer performance. Effects of diluent volume, nebulizer flow, and nebulizer brand. Chest. 1996;110:498-505 ↩

5. Cutglass DJ, Hampers L, Roosevelt G, et al. Undiluted albuterol aerosols in the paediatric emergency department. Paediatrics. 2000;105:67 ↩

6. Lahn M, Bijur P, Gallagher EJ. Randomised clinical trial of intramuscular versus oral methylprednisolone in the treatment of asthma exacerbations following discharge from an emergency department. Chest. 2004;126:362-8 ↩

7. Lazarinis N, Jørgensen L, Ekström T, et al. Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction. Thorax 2014;69:130-136.  ↩

8. Rowe BH, Spooner C, Ducharme FM, et al. Early emergency department treatment of acute asthma with systemic corticosteroids (Cochrane review) In: The Cochrane Library Issue 1,  2001. Oxford: Update Software ↩

9. Edmonds ML, Camargo CA, Pollack CV, et at. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. (Cochrane review) In: The Cochrane Library Issue 1,  2001. Oxford: Update Software ↩

10. Adams NP, Bestall JB, Jones PW. Inhaled beclomethasone versus placebo for chronic asthma. Cochrane Database Syst Rev. 2000(4 ↩

11. Straus SE, McAlister FA, Sackett DL, et al. The accuracy of patient history, wheezing, and laryngeal measurements in diagnosing obstructive airways disease. JAMA 2000;283:1853-7 ↩

12. Oshaug K, Halvorsen PA, Melbye H. Should chest examination be reinstated in the early diagnosis of chronic obstructive pulmonary disease? Int J Chron Obstruct Pulmon Dis. 2013;8:369-77. doi: 10.2147/COPD.S47992. Epub 2013 Jul 31. PMID: 23983462; PMCID: PMC3751499. ↩

13. Shorr AF, Sun X, Johannes RS, et al. Validation of a novel risk score for severity of illness in acute exacerbations of COPD. Chest 2011;140:1177-1183 ↩

14. Davies L, Angus RM, Claverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet. 1999;354:456-460 ↩

15. Bhatta L, Leivseth L, Mai XM, Henriksen AH, Carslake D, Chen Y, Langhammer A, Brumpton BM. GOLD Classifications, COPD Hospitalization, and All-Cause Mortality in Chronic Obstructive Pulmonary Disease: The HUNT Study. Int J Chron Obstruct Pulmon Dis. 2020 Jan 31;15:225-233. doi: 10.2147/COPD.S228958. PMID: 32099347; PMCID: PMC6999582. ↩

16. Ni H, Aye SZ, Naing C. Magnesium sulfate for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2022 May 26;5(5):CD013506. doi: 10.1002/14651858.CD013506.pub2. PMID: 35616126; PMCID: PMC9134202. ↩

17. Kew KM, Mavergames C, Walters JAE. Long‐acting beta₂‐agonists for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD010177. DOI: 10.1002/14651858.CD010177.pub2. Accessed 14 February 2023. ↩

18. Davies L, Nisar M, Pearson MG, et al. Oral corticosteroid trials in the management of stable chronic obstructive pulmonary disease. Q J Med. 1999;92:395-400 ↩

19. Rabe KF. Treating COPD – the TORCH trial, p-values and the dodo. N Engl J Med. 2007;356:851-4 ↩

20. Ram FS, Jones PW, Castro AA, et al. Oral theophylline for chronic obstructive pulmonary disease. The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd ↩

21. Shuai T, Zhang C, Zhang M, Wang Y, Xiong H, Huang Q, Liu J. Low-dose theophylline in addition to ICS therapy in COPD patients: A systematic review and meta-analysis. PLoS One. 2021 May 24;16(5):e0251348. doi: 10.1371/journal.pone.0251348. PMID: 34029327; PMCID: PMC8143407. ↩

22. Barr RG, Rowe BH, Camargo CA. Methylxanthines for exacerbations of  chronic obstructive pulmonary disease: meta-analysis of randomised trials. BMJ. 2003;327:643-6 ↩

23. Dobler CC, Morrow AS, Beuschel B, Farah MH, Majzoub AM, Wilson ME, Hasan B, Seisa MO, Daraz L, Prokop LJ, Murad MH, Wang Z. Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-analysis. Ann Intern Med. 2020 Mar 17;172(6):413-422. doi: 10.7326/M19-3007. Epub 2020 Feb 25. PMID: 32092762. ↩

24. Crockett AJ, Cranston JM, Moss JR, et al. Domiciliary oxygen for chronic obstructive pulmonary disease (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd ↩

25. Nocturnal Oxygen Therapy Trial (NOTT) Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease.  Ann Intern Med. 1980;93:391-8 ↩

26. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis. Lancet. 1981;1:681-6 ↩

27. The LOTT Research Group. A randomised trial of oxygen therapy for COPD with moderate desaturation. Nw Engl J Med 2016;375:1617-1627. doi 10.1056/NEJMoal604344  ↩

28. Hartmann-Boyce J, Chepkin SC, Ye W, Bullen C, Lancaster T. Nicotine replacement therapy versus control for smoking cessation. Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No.: CD000146.DOI: 10.1002/14651858.CD000146.pub5 ↩

29. Cigarette smoking among adults – United States 1999. MMWR Morb Mortal Wkly Rep. 2001;50:869-73 ↩

30. Fiore MC, Hatsukami DK, Baker TB. Effective tobacco dependence treatment. JAMA. 2002;288:1768-71 ↩

31. Sutherland ER, Cherniack RM. Management of chronic obstructive pulmonary disease. N Engl J Med. 2004;350:2689-97 ↩

32. Anthonisen NR, Skeans MA, Wise RA, et al. The effects of a smoking cessation intervention on 14.5-year mortality. Ann Intern Med. 2005;142:233-9 ↩

33. Nichol KL, Margolis KL Wuorenma J, et al. The efficacy and cost-effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med. 1994;331:778-84 ↩

34. Durrington HJ, Flubacher M, Ramsay CF, et al. Initial oxygen management in patients with an exacerbation of chronic obstructive pulmonary disease. Q J Med. 2005;98:499-504 ↩

Was this article helpful?

0 out Of 5 Stars

5 Stars		0%
4 Stars		0%
3 Stars		0%
2 Stars		0%
1 Stars		0%

5 Submit

Send Feedback

How can we improve this article?

Please submit the reason for your vote so that we can improve the article.

Submit