Importance of inhaler devices in the management of airway disease.

The delivery of drugs by inhalation is an integral component of asthma and chronic obstructive pulmonary disease (COPD) management. However, even with effective inhaled pharmacological therapies, asthma, particularly, remains poorly controlled around the world. The reasons for this are manifold, but limitations of treatment guidelines in terms of content, implementation and relevance to everyday clinical life, including insufficient patient education, access to health care and cost of medication as well as poor inhaler technique are likely to contribute. Considering that inhalation therapy is a cornerstone in asthma and COPD management, little advice is provided in the guidelines regarding inhaler selection. The pressurised metered dose inhaler (pMDI) is still the most frequently prescribed device worldwide, but even after repeated tuition many patients fail to use it correctly. In addition, the correct technique can be lost over time. Although several improvements in pMDIs such as a change in the propellant and actuation have resulted in improvements in lung deposition, many dry powder inhalers (DPIs) are easier to use. However, these devices also have limitations such as dependency of drug particle size on flow rate and loss of the metered dose if the patient exhales through the device before inhaling. Improvements in using inhalation devices more efficiently, in inhaler design for supporting patient compliance, and advances in inhaler technology to assure drug delivery to the lungs, have the potential to improve asthma and COPD management and control. New and advanced devices are considered being helpful to minimise the most important problems patients have with current DPIs.

The need to improve inhalation technique in Europe: a report from the Aerosol Drug Management Improvement Team.

Although the principles of asthma management are well established in Europe, the available data indicate that asthma in patients is not well controlled. Many patients derive incomplete benefit from their inhaled medication because they do not use inhaler devices correctly and this may compromise asthma control. The Aerosol Drug Management Improvement Team (ADMIT), incorporating clinicians from the UK, Germany, France, Italy, Spain and The Netherlands, reviewed published evidence to examine ways to improve the treatment of reversible airways disease in Europe. Data indicate that there is a clear need for specific training of patients in correct inhalation technique for the various devices currently available, and this should be repeated frequently to maintain correct inhalation technique. Devices which provide reassurance to patients and their physicians that inhalation is performed correctly should help to improve patient compliance and asthma control. Educational efforts should also focus on primary prescribers of inhaler devices. ADMIT recommends dissemination of information on the correct inhalation technique for each model of device by the use of an accessible dedicated literature base or website which would enable to match the appropriate inhaler to the individual patient. There is also a need for standardisation of prescribing practices throughout Europe. Regular checking of inhalation technique by prescribers is crucial as correct inhalation is one of the keystones of successful asthma management.

Inhaler technique: facts and fantasies. A view from the Aerosol Drug Management Improvement Team (ADMIT).

Health professionals tasked with advising patients with asthma and chronic obstructive pulmonary disease (COPD) how to use inhaler devices properly and what to do about unwanted effects will be aware of a variety of commonly held precepts. The evidence for many of these is, however, lacking or old and therefore in need of re-examination. Few would disagree that facilitating and encouraging regular and proper use of inhaler devices for the treatment of asthma and COPD is critical for successful outcomes. It seems logical that the abandonment of unnecessary or ill-founded practices forms an integral part of this process: the use of inhalers is bewildering enough, particularly with regular introduction of new drugs, devices and ancillary equipment, without unnecessary and pointless adages. We review the evidence, or lack thereof, underlying ten items of inhaler 'lore' commonly passed on by health professionals to each other and thence to patients. The exercise is intended as a pragmatic, evidence-informed review by a group of clinicians with appropriate experience. It is not intended to be an exhaustive review of the literature; rather, we aim to stimulate debate, and to encourage researchers to challenge some of these ideas and to provide new, updated evidence on which to base relevant, meaningful advice in the future. The discussion on each item is followed by a formal, expert opinion by members of the ADMIT Working Group.

Erratum: Inhaler technique: facts and fantasies. A view from the Aerosol Drug Management Improvement Team (ADMIT).

[This corrects the article DOI: 10.1038/npjpcrm.2016.17.].

Benzodiazepine-opiate antagonism--a problem in intensive-care therapy.

A 14-year-old previously fit schoolboy was admitted with staphylococcal pneumonia secondary to influenza A infection. His condition deteriorated as he developed adult respiratory distress syndrome (ARDS); during a stormy recovery exceptionally high doses of benzodiazepines and opiates were given in order to suppress voluntary breathing during a successful period of assisted ventilation. It is possible that benzodiazepine-opiate antagonism developed. Subsequent studies in laboratory mice indicate that the respiratory depressant effects of morphine can be antagonized by prior treatment with lorazepam.

Phase II trial of vindesine and VP16-213 in the palliation of poor-prognosis patients and elderly patients with small cell lung cancer.

Forty-three previously untreated patients, all of whom had poor-prognosis small cell lung cancer and/or were greater than 65 years old, received treatment with vindesine and VP16-213. Thirteen patients had limited disease and 30 extensive disease. Response rates (CR + PR) of 86% (CR 29%) and 66% (CR 17%) were seen in patients with limited and extensive disease, respectively. Time to relapse was short in those responding (4-4.5 months), and most responders required additional treatments. The overall toxicity was minimal and patient compliance was high. This combination is useful for the palliative treatment of small cell lung cancer when aggressive chemotherapy is inappropriate.

Evaluation of the combination inhaler of salbutamol and beclomethasone dipropionate in the management of asthma.

An open parallel study lasting 24 weeks was performed in 39 asthmatics to evaluate patient compliance and the clinical effects of regular inhalations of beclomethasone dipropionate and salbutamol used simultaneously from a combination inhaler with regular inhalations of salbutamol and beclomethasone dipropionate used sequentially from separate inhalers. Total daily doses in the two groups were 800 micrograms salbutamol and 400 micrograms beclomethasone dipropionate. There were no differences between the two treatment groups with respect to clinic pulmonary function tests (FEV1, FVC), daily PEF measurements, symptom scores, use of symptomatic bronchodilator therapy, requirements for extra medication and patients' and physician's assessment of treatment. At 12 weeks, the physician assessed significantly more patients to have better symptom control on the combination inhaler than on separate inhalers. Patient compliance was high in both treatment groups which may have been due to the close supervision of the clinical study.

Inappropriate inhaler use: assessment of use and patient preference of seven inhalation devices. EDICI.

Inefficient inhaler technique is a common problem resulting in poor drug delivery, decreased disease control and increased inhaler use. The aim of this study was to assess patients' use of different inhaler devices and to ascertain whether patient preference is indicative of ease of use and whether current inhaler use has any influence on either technique or preference. We also wished to define the most appropriate method of selecting an inhaler for a patient, taking into account observed technique and device cost. One hundred patients received instruction, in randomized order, in the use of seven different inhaler devices. After instruction they were graded (using predetermined criteria) in their inhaler technique. After assessment patients were asked which three inhalers they most preferred and which, if any, they currently used. Technique was best using the breath-actuated inhalers; the Easi-Breathe and Autohaler, with 91% seen to have good technique. The pressurized metered dose inhaler (pMDI) fared poorly, in last position with only 79% of patients showing good technique, despite being the most commonly prescribed. The Easi-Breathe was by far the most popular device with the patients. The Autohaler came in second position closely followed by the Clickhaler and Accuhaler. The majority of patients (55%) currently used the pMDI but the pMDI did not score highly for preference or achieve better grades than the other devices. Only 79% of patients tested could use the pMDI effectively even after expert instruction yet it continues to be commonly prescribed. This has important repercussions for drug delivery and hence disease control. Prescribing a patient's preferred device increases cost but can improve efficiency and therefore be cost effective in the long term. Using an inexpensive device (pMDI) when technique is good and the patient's preferred inhaler device when not is one way to optimize delivery and may even reduce cost.

Peak inspiratory flow through Turbuhaler in chronic obstructive airways disease.

Many patients with chronic obstructive airways disease (COAD) receive therapy by the inhaled route. This study was performed to assess whether patients with severe COAD could generate sufficient peak inspiratory flow (PIF) through Turbuhaler (Astra, Sodertalje) to operate it effectively. One hundred patients (45 men, 55 women, mean age 69.1 years) with COAD (mean (SD) duration 17.7 (16.3) years) and peak expiratory flow (PEF) < or = 200 l min-1 or forced expiratory volume in 1 sec (FEV1) < or = 1 litre were studied. A series of randomly assigned inspiratory and expiratory lung function tests were contiguously performed, using portable spirometers, within 48 h of a screening visit. An empty Turbuhaler was used in the study. The patients' normal medication was not restricted. Sixty-six patients were previous smokers, eight occasional smokers, 19 habitual smokers and seven had never smoked. Mean (SD) FEV1 was 0.7 (0.2) 1 and mean PEF was 182 (68) l min-1. All patients were able to generate PIF through Turbuhaler (PIF-T) of 28 l min-1 (mean 53; range 28-78 l min-1). Eighty-three patients generated PIF-T of > or = 40 l min-1. PIF-T correlated with PIF without Turbuhaler (r = 0.35), PEF (r = 0.3), FEV1 (r = 0.2) and forced vital capacity (FVC) (r = 0.23) although the relationships were too weak to be used to predict PIF-T. The results suggest that patients with severely limited lung function caused by COAD can operate Turbuhaler effectively.

Starting home nebulizer therapy: patients' expectations and subsequent outcome at 2 months.

Twenty-six patients with severe COPD or asthma completed standard questionnaires before, and 2 months after, starting home nebulized bronchodilator therapy. Patients' perceived illness severity and their expectations of treatment with regard to symptoms were examined in the first questionnaire, and outcome was assessed in the second. Before treatment started patients expected a definite improvement in all symptoms studied. After treatment the group showed only a marginal subjective improvement in all symptoms. The improvement attained with regard to breathlessness, ability to get out and about, and general quality of life was significantly lower than had been expected. While home nebulized bronchodilator therapy is well tolerated and confers some subjective benefit in selected individuals, patients appear to have unrealistically high expectations of treatment.

Hypothalamo-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids.

The frequency of hypothalamo-pituitary-adrenal (HPA) axis suppression in asthmatics taking high dose (greater than 1000 micrograms daily) inhaled corticosteroids is unknown. HPA function was studied in 78 adult asthmatics taking long-term inhaled corticosteroids (median dose 1600 micrograms, range 1200-2650 micrograms daily). All patients except one were using metered dose aerosols; 15 were using large volume spacer devices. Median duration of high dose therapy was 13 months (range 1-54). Sixty-nine patients were taking beclomethasone dipropionate (1500 micrograms, n = 36; 2000 micrograms, n = 26, greater than 2000 micrograms, n = 7) and nine budesonide (1200 micrograms, n = 2; 1600 micrograms, n = 6; 1800 micrograms, n = 1). Four patients, all of whom were taking greater than 2000 micrograms beclomethasone dipropionate, were taking 200-400 micrograms of their total dose intranasally. Twenty-six patients had discontinued long term systemic corticosteroid treatment (at least 5 mg prednisolone daily, or equivalent, for a minimum of 6 months) between 7 months and 22 years prior to assessment. All patients had measurements of 9 am serum cortisol and 24-h urine free cortisol excretion and a short tetracosactrin test. Subnormal results were: 9 am cortisol less than 190 nmol l-1; rise in serum cortisol in response to tetracosactrin less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1; urine free cortisol less than 80 nmol 24 h-1. Hypothalamo-pituitary-adrenal suppression was defined as subnormal results in at least two of the three tests. Tests were performed at least 2 weeks after completion of any short course prednisolone treatments. Suppression was found in 16 (20.5%) patients (1500 micrograms, n = 6; 1600 micrograms, n = 1; 2000 micrograms, n = 7; 2400 micrograms, n = 2). Risk factors identified for this suppression were: (a) previous requirement for long-term systemic corticosteroids (10/26, chi 2 = 6.1, P less than 0.02); and (b) increasing duration of high dose inhaled therapy (median 28.5 months in suppressed vs. 12 months in normal, P less than 0.05). No clear relationship was identified between HPA function and dose, even when corrected for body surface area and there was no relationship between suppression and number of short courses of prednisolone in the preceding 12 months. Screening tests of HPA function should be performed in all asthmatics taking greater than or equal to 1500 micrograms inhaled corticosteroid daily. Unless function has been shown to be normal, all patients taking these doses should carry steroid cards.

Screening for hypothalamo-pituitary-adrenal axis suppression in asthmatics taking high dose inhaled corticosteroids.

High dose inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal (HPA) axis. Several tests are available to screen for this suppression but it is not clear which is the most useful. HPA function was assessed in 78 adult asthmatics inhaling long-term, high dose (median 1600 micrograms; range 1200-2650 micrograms) beclomethasone dipropionate (n = 69) or budesonide (n = 9). Screening tests performed in all patients were 9 am serum cortisol, short tetracosactrin test and 24-h urine free cortisol excretion. Eleven patients also underwent insulin stress tests. Subnormal results were: 9 am cortisol less than 190 nmol l-1; urine free cortisol less than 80 nmol 24 h-1; rise in cortisol in response to tetracosactrin or hypoglycaemia less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1. HPA suppression (defined as subnormal results of at least two of the three initial tests and/or subnormal response to hypoglycaemia), was found in 16 patients. In the 11 patients who underwent insulin stress tests, results of all initial tests were normal in three, one test was abnormal in three and two tests were abnormal in four patients. All three tests were abnormal in the remaining patient. The response to hypoglycaemia was normal in the three patients whose screening tests were all normal; HPA suppression was present in seven patients and one patient had a borderline result. Close correlation was observed between the maximum cortisol during hypoglycaemia and both urine free cortisol (rs = 0.84; P = 0.001) and post-tetracosactrin cortisol (r = 0.75; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

High dose inhaled steroid therapy and the cortisol stress response to acute severe asthma.

Systemic absorption of inhaled corticosteroids taken in high doses (> or = 1500 micrograms beclomethasone dipropionate or budesonide daily), may cause suppression of the hypothalamo-pituitary-adrenal axis. Patients taking long-term high dose inhaled steroid therapy might therefore be at risk of adrenal crisis at times of stress. Plasma cortisol levels were measured in 24 adults with severe acute asthma who had not received treatment with systemic corticosteroids prior to hospital attendance. Seven were not taking inhaled steroids, four were taking 600-1200 micrograms and 13 were taking 1500-2400 micrograms beclomethasone dipropionate or budesonide daily. Plasma cortisol levels in these 13 (median 594 nmol l-1, interquartile range 399-620 nmol l-1) were similar to levels in those taking lower dose/no inhaled steroids (median 512 nmol l-1, interquartile range 287-1050 nmol l-1): there was no relationship between inhaled steroid dose and cortisol level. Nine of the 24 patients failed to achieve plasma cortisol values > 500 nmol l-1 (the normal response to an insulin stress test). When compared with the remaining 15, they had less severe asthma as indicated by higher arterial oxygen tension (P < 0.01) and peak expiratory flow (P < 0.03). Patients taking long-term high dose inhaled corticosteroids appear to be able to mount an appropriate adrenocortical response to the stress of severe acute asthma.

The Spacehaler for delivery of salbutamol: a comparison with the standard metered-dose inhaler plus Volumatic spacer device.

The Spacehaler is a new, compact, pressurized aerosol device that uses the same canister as a conventional metered-dose inhaler (MDI). Its design, however, reduces the velocity of the aerosol cloud that emerges from the inhaler, thereby reducing the amount of the non-respirable fraction of the drug delivered to the patient. Large volume spacers achieve a similar effect, but they are bulky and therefore inconvenient to use and carry around. This study compared the bronchodilator effect of 200 micrograms salbutamol delivered by the Spacehaler to that of an MDI used with a Volumatic spacer (MDI plus spacer) in patients with reversible obstructive airways disease. Twenty-five patients with asthma, having a forced expiratory volume in 1 s (FEV1) between 50 and 90% predicted and a reversibility of > or = 15% to 200 micrograms salbutamol given by the conventional (standard) MDI entered the study. On two separate study days, they inhaled 200 micrograms salbutamol either via the Spacehaler or the MDI plus spacer. To maintain blinding, they received placebo on both study days via the alternate device. Their FEV1, forced vital capacity (FVC) and peak expiratory flow (PEF) were measured before and at regular intervals for 6 h after inhalation. Assessment of equivalence between the two devices was based on whether the 90% confidence interval for the difference between the weighted mean FEV1 was within +/- 0.25 1. Patient preference was assessed by a questionnaire at the end of the second study day. Twenty-four patients completed the study. Both devices produced a significant improvement in FEV1 (P < 0.02). The upper and lower 90% confidence limits for the difference in weighted mean FEV1 between the devices was +/- 0.041, and the 99% confidence limits were +0.061 and -0.071. The weighted means for FVC and PEF, and the duration of effect and peak responses for FEV1, FVC and PEF also showed no difference between the two devices. Patients found no difficulty in using the Spacehaler, and 20 out of 24 patients (83.3%) preferred it to the MDI plus spacer. The bronchodilator effect of 200 micrograms salbutamol administered by a Spacehaler was equivalent to that produced by an MDI plus spacer in this group of patients with reversible airways obstruction. The majority of patients preferred it to a large volume spacer.

Pulmonary eosinophilia with systemic features: therapy and prognosis.

Of 65 patients presenting with pulmonary eosinophilia to one Respiratory Unit during a 20-year period, 12 (18%) had systemic features associated with their pulmonary disease. Eleven had fever, three night sweats, three arthralgia, three vasculitic rashes and two weight loss. Anaemia, myalgia, peripheral neuropathy, mononeuritis, pericardial effusion and photosensitivity rash were each recorded in single patients. None had evidence of hypersensitivity to drugs, helminthes or other allergens. Ten of the 12 patients could be classified as cryptogenic pulmonary eosinophilia and two as Churg Strauss syndrome. Ten were female. The maximum recorded eosinophil counts were higher in the 12 patients with systemic features compared with the remaining 53 patients [mean (SD) 5613 (3883) vs. 2359 (3046) x 10(6) 1(-1), P < 0.02], whereas both asthma and recurrent episodes of eosinophilia were significantly less common. Steroid therapy achieved a good clinical response and radiological clearing in the majority of patients. All 12 patients were treated with prolonged duration oral prednisolone [mean (SEM) dose 8.5 (3.8) mg day-1 duration 5.5 (1.3) years]. The two patients with Churg Strauss syndrome required azathioprine in addition to long-term prednisolone. There were no deaths and currently four patients are off all steroids and six receive less than 5 mg day-1. During a median follow-up period of 11 years, there was no significant decline in FEV1 or VC, measured as percent predicted values. Persistent radiographic abnormalities consistent with fibrosis or bronchiectasis were not seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory impairment in inflammatory bowel disease: does it vary with disease activity?

Serial assessments of respiratory function were made in 44 patients with inflammatory bowel disease. Pulmonary function tests were performed at the initial assessment and after three months to see if abnormality was associated with alteration in disease activity, drug therapy or with evidence of immunological disturbance. Fourteen patients (32%) had some abnormality of respiratory function when first investigated. Seven (16%) had a reduced gas transfer factor but these abnormalities were not related to disease activity, drug therapy or any immunological variable. Elevation of both functional residual capacity and residual volume was found in nine (20%) patients at the initial assessment. These abnormalities appeared to be associated with active inflammatory bowel disease and in four of these patients lung volumes returned to normal at 3 months when the bowel disease was in remission.

Comparison of Pulmicort pMDI plus Nebuhaler and Pulmicort Turbuhaler in asthmatic patients with dysphonia.

BACKGROUND: Dysphonia is a known local adverse effect of inhaled corticosteroids. This symptom was investigated by laryngoscopy and assessment in a voice laboratory. The effects of changing the treatment of patients with dysphonia, reported whilst using the pMDI, to pMDI plus Nebuhaler or Tubuhaler was also assessed. METHODS: Seventy-two patients reporting dysphonia and taking inhaled steroids from a pMDI entered a 12-week, open, parallel group study. Fifty-one completed the study per protocol; 26 in the Nebuhaler group [21 female, mean age 57 years (22-77)] and 25 in the Turbuhaler group [18 female, mean age 58 years (21-81)]. A dysphonia diary card was completed weekly. Voice laboratory assessments and laryngoscopy were performed on entry and at 12 weeks. RESULTS: There were no differences in voice laboratory data, laryngoscopic evidence of disordered glottic closure and diary data between the two groups at 12 weeks. At study entry laryngoscopic appearances were normal in almost half the patients. Vocal cord bowing was rarely seen. Glottic closure changed in nine patients during the study period, but there was no correlation with voice symptoms. The trend of symptomatic improvement of voice status in the Turbuhaler group did not correlate with voice laboratory assessments and laryngoscopic evidence of disordered glottic closure. After 4 weeks, 40% of patients using Turbuhaler and 8% in the Nebuhaler group scored their voice status as better (P < 0.02) but there was no significant difference between the two groups at 12 weeks (Turbuhaler 52%, Nebuhaler 23%, P=0.08). CONCLUSION: This study does not support the view that dysphonia in asthmatics inhaling corticosteroids is usually caused by myopathic bowing of the vocal cord muscles.

Prolonged Q fever associated with inappropriate secretion of anti-diuretic hormone.

A man with acute Q fever developed hyponatraemia associated with inappropriate secretion of anti-diuretic hormone. The pyrexial illness lasted for 9 weeks and failed to respond to tetracycline, erythromycin and intravenous lincomycin. Subsequently seroconversion indicated chronic Q fever.

Dry powder inhalers: advantages and limitations.

New inhalers have been developed because of difficulty of using the conventional metered dose inhaler (MDI) and because of the impending ban on CFC's. Dry powder inhalers (DPI's) in general are easier to use than the MDI and cause fewer irritant effects. Unlike the MDI few patients develop a poor inhalation technique with continued use of DPI's. Comparisons of multidose DPI's have shown that they achieve a similar degree of bronchodilatation to the MDI. Comparisons of the Diskhaler and Turbuhaler have shown little difference in therapeutic efficacy, but most indicate patient preference for the Turbuhaler. The inspiratory flow necessary to achieve a therapeutic effect is critical with DPI's. The majority of patients with severe acute asthma can achieve a peak inspiratory flow sufficient to inhale a bronchodilator from a Turbuhaler. DPI's cannot be used with spacers; this may be a disadvantage in patients who inhale large doses of steroids.

Non-Hodgkin's lymphoma of the lung.

Non-Hodgkin's lymphoma (NHL) commonly presents with extensive disease involving extranodal tissues. Involvement of the mediastinal and hilar lymph nodes, pleura and lung parenchyma are recognised complications although their incidence is uncertain. However, pulmonary involvement is undoubtedly much less common than involvement at other extra nodal sites. Histologically proven NHL limited to the lung parenchyma, after full staging including computerised tomography and marrow trephines, is extremely rare. We report on two such cases and review the literature.