Contents:
Tele-monitoring of ventilator-dependent patients: Prevention of COPD exacerbations: European Respiratory Society guidelines for the management of adult bronchiectasis. Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians. ERS statement on protracted bacterial bronchitis in children. PDF Additional material 2. ERS technical standard on bronchial challenge testing: European Respiratory Society statement: An official European Respiratory Society statement: ERS statement on obstructive sleep disordered breathing in 1- to month-old children.
European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia.
European Respiratory Society guidelines. General practitioners and rare lung diseases: Monitoring asthma in children. Research questions in COPD. Treatment of Idiopathic Pulmonary Fibrosis. Executive summary Full text Evidence tables Evidence-to-decision tables.
Smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit. Combined endobronchial and oesophageal endosonography for the diagnosis and staging of lung cancer. Diagnosis and treatment of primary spontaneous pneumothorax. ERS task force report. Interstitial pneumonia with autoimmune features. Multidisciplinary respiratory management of ataxia telangiectasia. Enhancing implementation, use, and delivery of pulmonary rehabilitation.
The European initiative for quality management in lung cancer care. Specific inhalation challenge in the diagnosis of occupational asthma. Expert opinion on the cough hypersensitivity syndrome in respiratory medicine. PDF Clinician survey Patient survey. Nutritional assessment and therapy in COPD: Consensus statement for inert gas washout measurement using multiple- and single-breath tests. Recommendations for the management of patients with obstructive sleep apnoea and hypertension.
Key Concepts and Advances in Pulmonary Rehabilitation. Guidelines for the management of work-related asthma. Clinical Microbiology and Infection. Guidelines for the management of adult lower respiratory tract infections. What the pulmonary specialist should know about the new inhalation therapies. Non-CPAP therapies in obstructive sleep apnoea. Evidence-based Guidelines for Diagnosis and Management. Standards for Quantitative Assessment of Lung Structure.
Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma.
Early stage and locally advanced non-metastatic non-small-cell lung cancer: Metastatic non-small-cell lung cancer: Global tuberculosis control Asthma Control and Exacerbations. Defining, treating and preventing hospital acquired pneumonia: Guidelines for the diagnosis and treatment of pulmonary hypertension. Guidelines for the management of community acquired pneumonia in adults: Definition, assessment and treatment of wheezing disorders in preschool children: Outcomes for COPD pharmacological trials: British Guideline on the Management of Asthma.
Guidelines for the programmatic management of drug-resistant tuberculosis. International Health Regulations End-of-life decision-making in respiratory intermediate care units: Pulmonary Function Testing in Preschool Children. ERS guidelines on the assessment of cough. Recommendations on the use of exercise testing in clinical practice. Smoking cessation in patients with respiratory diseases: Weaning from mechanical ventilation.
Diagnosis and Management of Lung Cancer: ACCP Guidelines 2nd edition. International Standards for Tuberculosis Care: Medical Therapy for Pulmonary Arterial Hypertension: Intermediate care—Hospital-at-Home in chronic obstructive pulmonary disease: British Thoracic Society guideline. Recommended standards for modern tuberculosis laboratory services in Europe.
Standardisation of lung function testing - General considerations for lung function testing. Standardisation of lung function testing - Interpretative strategies for lung function tests. Standardisation of lung function testing - Standardisation of spirometry. Standardisation of lung function testing - Standardisation of the measurement of lung volumes.
The authors concluded that oral corticosteroids improve CXR appearances after 6 to 24 months of treatment and result in small increases in vital capacity and diffusing capacity, although it is unclear whether these benefits persist after 2 years. These observations support the widespread view that steroids are not indicated in stage I disease unless lung function is declining.
The authors commented that there are no data suggesting that steroid treatment influences long-term disease progression. The starting dose of prednisolone in controlled studies has varied from 30 mg to 60 mg daily, usually tapering each month according to response, to an average of 10 mg daily maintained for 6 to 12 months before attempting slow withdrawal. Anecdotal observation suggests that in some patients, treatment is best continued for at least two years to prevent relapses. Alternate day dosing with the dose kept equivalent to the average daily dose has been suggested to limit side-effects 18 and shown in a controlled study to be as effective as daily treatment.
Selroos and colleagues first reported the value of inhaled budesonide in an open study of 20 patients with pulmonary sarcoidosis. Only two studies, using budesonide, showed benefit. A more recent study 21 compared outcomes after three months of prednisone followed by 15 months of inhaled budesonide with placebo. Corticosteroid therapy was of benefit, especially for those with parenchymal disease, and the benefit persisted for five years after stopping treatment.
Taken together, current evidence thus suggests that inhaled steroids are less consistently effective than oral steroids in pulmonary sarcoidosis. This is unsurprising since they target the airways rather than the lung parenchyma, and it is generally agreed they should not be employed routinely.
A number of recent studies indicate that adverse events such as weight gain, skin thinning, sleep disturbance, osteoporosis and neuropsychiatric disorders occur not infrequently in patients taking corticosteroids, even in low dose. Steroid-induced diabetes is also a significant risk. There are no specific guidelines on monitoring for adverse effects in sarcoidosis. Although serious adverse effects may occur without warning, some are potentially preventable by using the lowest steroid dose possible, careful monitoring, and appropriate prophylaxis.
National formularies contain general prescribing information, and various professional organizations and charities provide patient information. Evidence-based guidelines for preventing and treating osteoporosis have been published in several countries, mainly but not exclusively in Europe and North America. The American College of Rheumatology ACR recommends several interventions for preventing bone loss and fractures in patients taking prednisolone at a dose of 5 mg daily or more for over 3 months.
These guidelines advise replacing gonadal steroids in men if deficient, and using calcitonin if bisphosphonates are contraindicated or not tolerated. They recommend annual follow-up and initiation of an exercise program where possible. They also advise hour urinary calcium excretion estimation where the above measures are instituted because of the risk of hypercalcuria with glucocorticosteroids.
Azathioprine is metabolized by the enzyme thiopurine methyltransferase TPMT , and the risk of myelosuppression is increased in the minority of the population who are homozygous for low TPMT activity. Smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit. European Respiratory Society Guidelines on the use of nebulizers. Prophylaxis against pneumonia caused by Pneumocystis jiroveci should be given to all patients with a history of the infection, and should be considered for severely immunocompromised patients. Depressed cutaneous delayed-type hypersensitivity explains the typically negative tuberculin test. TPMT testing before azathioprine therapy.
UK guidelines on the management of glucocorticoid-induced osteoporosis, 28 endorsed by a number of national specialist medical societies including the BTS, advise measurement of bone mineral density BMD to assess fracture risk in patients in whom there is a history of exposure to, or an intention to treat with, oral corticosteroids for three months or more. In those with a history of fracture, other secondary causes of osteoporosis should also be excluded. In those without a previous fracture and a T score above 0, reassurance and general measures are advised, and repeat BMD measurement is not indicated unless exceptionally high doses of glucocorticoids are required, as in for instance intravenous methyl prednisolone protocols.
General measures include reducing the steroid dose where possible and considering a steroid-sparing agent, nutritional advice with particular regard to calcium and vitamin D intake, regulating body weight, smoking cessation and avoiding alcohol excess, and assessing falls risk with further advice as appropriate.
Specific treatments include alendronate, alfacalcidol, calcitonin, calctritiol, clodronate, cyclical etidronate, hormone replacement therapy, pamidronate and risedronate. Adler and Hochberg address certain issues particularly relevant in sarcoidosis. Afro-Americans make up a large proportion of the sarcoidosis population and may be at reduced risk of glucocorticoid-induced osteoporosis. These authors therefore advise measuring baseline serum and urine calcium and repeating measurements 4 to 8 weeks after starting calcium supplements, with subsequent monitoring.
A study of BMD in women with sarcoidosis has shown that post-menopausal controls had higher BMD than untreated patients with sarcoidosis, suggesting that post-menopausal patients with sarcoidosis may be at increased risk of bone mineral loss. First reported in , hundreds of cases of bisphosphonate-associated osteonecrosis of the mandible have now been described worldwide.
Most cases have been associated with intravenous pamridonate and zoledronic acid, and length of treatment is a further risk factor, especially over 36 months. An initial dental examination with appropriate preventative dentistry should be considered before starting; while patients with concomitant risk factors should avoid invasive dental procedures while on treatment if possible.
A further consideration in sarcoidosis is that patients are relatively young, with females often of reproductive age. Since manufacturers advise against using bisphosphonates in pregnancy, physicians must either not prescribe these agents in females of child-bearing age or counsel them appropriately. A number of patients with severe or persistent sarcoidosis require treatment with alternative agents, usually in combination with corticosteroids but sometimes alone, either in those for whom corticosteroids are contra-indicated, or in those unable to tolerate the side-effects of steroids.
Most of the published literature examining these agents consists of small case series with significant potential for bias, and many have primarily investigated the effects of these agents on extra-pulmonary, rather than pulmonary, disease. Only the most commonly used agents are reviewed here.
Methotrexate has been employed as a steroid-sparing agent for many years in the treatment of rheumatoid arthritis, and has recently emerged as one of the preferred second-line drugs for treating sarcoidosis.
It is a folic acid analogue which inhibits dihydrofolate reductase and trans-methylation reactions. At low doses it has anti-inflammatory properties attributed largely to enhanced release of adenosine. A randomized controlled trial of methotrexate 10 mg once weekly or placebo plus oral prednisolone in 24 patients, conducted over 1 year, showed that patients taking methotrexate required significantly less prednisolone in the second 6-month period.
Lung function, radiology and symptoms did not differ between the two groups. Aside from teratogenicity, the major side-effects are hepatotoxicty and bone marrow suppression, and regular monitoring of liver function and full blood count is thus vital. There is uncertainty around the value of surveillance liver biopsy in patients exposed to methotrexate for prolonged periods. Many authors recommend co-treatment with folic acid to limit toxicity.
A typical protocol is folic acid 5 to 10 mg once weekly, taken the day after methotrexate. Pregnancy should be excluded in females before starting treatment, and male and female patients receiving methotrexate must employ effective contraception. UK authorities advise continued contraception for at least three months after stopping the drug in males and females.
North American advice is that pregnancy should be avoided for at least 3 months after treatment in male patients, and for at least one ovulatory cycle in females. Patients who experience troublesome systemic upset after taking the drug may benefit from dividing the once weekly dose into two twice weekly doses.
Azathioprine is a purine analogue which has been shown in case series to improve chest x-ray appearances and breathlessness. Cellular immunity is suppressed to a greater degree than humoral immunity. There are no randomized controlled trials of azathioprine in sarcoidosis. A retrospective review suggested benefit in only 2 out of 10 patients, 33 while an open study analyzing 11 patients with chronic sarcoidosis treated with both azathioprine and prednisolone did suggest benefit.
Cytokine release in bronchoalveolar lavage was reduced. The authors commented that a larger study was required to answer definitively whether azathioprine might be an effective steroid-sparing agent in sarcoidosis; a decade later such a study remains to be conducted. Regular blood counts to check for myelosuppression, and liver function monitoring, are essential in patients taking azathioprine. Azathioprine is metabolized by the enzyme thiopurine methyltransferase TPMT , and the risk of myelosuppression is increased in the minority of the population who are homozygous for low TPMT activity.
Consequently many authors advise testing for TPMT levels before starting azathioprine, despite a paucity of evidence to support this practice. Hydroxychloroquine like chloroquine is an anti-malarial agent. Two randomized controlled trials have compared chloroquine and placebo in pulmonary sarcoidois. Chloroquine treatment conferred no benefit and greater side-effects.
In the recent, Canadian, study, 23 patients received chloroquine mg daily for 6 months, gradually tapering every two months to mg daily. Eighteen patients were then randomized to a maintenance group or to an observation group. Patients randomized to the maintenance group had a slower decline in lung function and fewer relapses than those in the observation group. Side-effects were mainly limited to the high dose treatment phase. The authors conclude that chloroquine should be considered in chronic pulmonary sarcoidosis; in practice, hydroxychloroquine is preferred because it has lower ocular toxicity.
Hydroxychloroquine should be used with caution in liver or renal impairment, and regular blood count monitoring to check for agranulocytosis and thrombocytopenia and liver function is needed. The British Royal College of Ophthalmologists advises that patients should be asked about visual impairment before starting treatment, and that visual acuity should be measured and recorded. If eye disease is present, an ophthalmologist should be consulted before starting treatment. Patients should be asked about visual symptoms during treatment and visual acuity monitored annually.
If treatment is required for over 5 years, individual arrangements should be made with the local ophthalmology service. Hydroxychloroquine should be used in caution in glucosephosphate G6PD deficiency as it may precipitate acute hemolytic anemia. As deficiency is highly prevalent in Africans, in whom persistent and severe sarcoidosis is more common, many physicians check G6PD levels before starting hydroxychloquine.
Cyclosporin A is a T cell suppressor which has been reported to improve neurosarcoidosis in two retrospective studies. However, a randomized controlled trial in 37 patients with pulmonary sarcoidosis treated over 18 months showed no benefit in terms of breathlessness or lung function, and side-effects were significantly greater in the treatment group.
Cyclophosphamide is an alkylating agent which has been used with apparent benefit in cardiac and neurosarcoidosis, but there are no controlled studies in pulmonary disease. Routine use cannot therefore be recommended. Mycophenolate mofetil MMF is an antiproliferative immunosuppressant like azathioprine, but is metabolized to mycophenolic acid, which has a more selective action than azathioprine. Several authors report employing MMF successfully as a steroid-sparing agent in extra-pulmonary sarcoidosis, but there are no controlled studies in pulmonary disease, and there are therefore currently insufficient data to recommend its use.
Individual case reports and small series support the use of thalidomide in cutaneous sarcoidosis, but there are no studies in pulmonary disease. Teratogenic concerns strictly limit its drug in women of child-bearing age, and side-effects can be troublesome. Pentoxifylline in high doses has been shown to improve lung function in mild pulmonary sarcoidosis.
Since then a series of case reports and small series have reported the effectiveness of infliximab for treating various manifestations, including skin, eye, brain, lung, sinus and muscle involvement. Two larger studies were reported in The first, by Doty and colleagues, 40 was a retrospective study of ten patients with sarcoidosis refractory to conventional agents. Six patients had lung involvement although the indication for using infliximab in these patients was extra-pulmonary disease.
Nine patients reported symptomatic improvement with infliximab treatment, and all demonstrated objective evidence of improvement. In five of six patients taking concomitant corticosteroids the dose was reduced. The authors did not comment on lung function or radiology.
They nevertheless concluded that infliximab appeared safe and effective in refractory sarcoidosis. The second study, conducted by Baughman and colleagues, 41 was a phase II, multi-center, double-blind, placebo-controlled clinical trial in which patients were randomized in a 1: Patients were followed through to week In all cases the indication for entering the study was refractory pulmonary disease. Patients in the infliximab groups combined had a mean increase in forced vital capacity FVC of 2.
Post-hoc exploratory analyses suggested that patients with more severe disease longer disease duration, lower FVC or more symptoms seemed to benefit the most. Although these benefits appear modest, they would be significant in patients with life-threatening fibrotic disease who would potentially also be candidates for transplantation. Even stability in such patients represents a significant treatment response, and improvement would be exceptional.
Etanercept has not been found to be as effective in sarcoidosis, possibly because infliximab achieves greater tissue penetration and cell mediated lysis of TNF-secreting cells.
Infliximab may therefore be considered in life-threatening pulmonary sarcoidosis when all other options have been exhausted. It is expensive, and patients need careful assessment beforehand for evidence of tuberculosis. Opportunistic infections are a potential consequence of immunosuppression.
Prophylaxis against pneumonia caused by Pneumocystis jiroveci should be given to all patients with a history of the infection, and should be considered for severely immunocompromised patients. North American guidelines for preventing opportunistic infection in HIV-infected individuals, 42 endorsed by the British Infection Society, provide the basis for current recommendations.
Oral co-trimoxazole is the drug of choice for prophylaxis, either mg daily or three times a week. The dose can be reduced to mg daily to improve tolerance. In patients unable to tolerate co-trimoxazole, nebulized pentamidine is effective, as is oral dapsone; atovaquone has also been employed. Co-trimoxazole and dapsone can cause bone marrow suppression and skin rashes among other side-effects. Neither North American nor British sarcoidosis guidelines recommend pneumocystis prophylaxis routinely in otherwise immuno-competent patients.
A small number of patients with severe and progressive pulmonary sarcoidosis, despite exhaustive medical therapy, may be candidates for transplantation. Patients must be assessed for the potential presence of bronchiectasis, right ventricular impairment, infection, and mycetomas before proceeding.
Possible reasons include reduced access to healthcare before and after surgery, increased graft loss due to immunological hyper-responsiveness, and greater major histocompatibility polymorphism. Similar findings are reported in the setting of renal and liver transplantation.
The authors concluded that patients with progressive symptomatic disease, or asymptomatic patients with infiltrates on CXR and progressively worsening lung function, should probably be treated. It suggests that inhaled steroids may be of value in airway disease. In patients who fail to respond to steroids after three months, it suggests considering other reasons for failure such as the presence of irreversible fibrosis, noncompliance, or inadequate dosage.
The British Thoracic Society BTS interstitial lung disease ILD 16 guidelines conclude that treatment is not indicated for asymptomatic stage I disease, nor in asymptomatic patients with stage II or III disease with mild lung function abnormalities and stable parameters. They recommend oral corticosteroids as first-line therapy in patients with disease progression as indicated by radiology or lung function or significant symptoms.
The authors recommend an initial dose of 0.
Inhaled steroids are not recommended as initial or maintenance treatment, but may be considered for symptom control in patients with troublesome cough. Table 2 summarizes the main points from the two guidelines. Bisphosphonates are advised as appropriate to minimize steroid-induced osteoporosis. Alternative immunosuppressants are recommended when corticosteroids are not controlling the disease or when side effects are intolerable, with methotrexate the agent of choice. Since low carbon monoxide transfer factor TLCO measurements predict survival in interstitial lung disease, they are a useful guide to the timing of referral for lung transplantation.
In summary, there is agreement that oral corticosteroids should be considered in patients with severe, persistent or progressively worsening respiratory symptoms, or declining lung function. Many physicians would monitor lung function VC and TLCO for 6 months before deciding that there is progressive deterioration.
There is agreement that neither oral nor inhaled corticosteroids are indicated in asymptomatic patients in the absence of other organ involvement. There is agreement that, provided the patient responds, the dose should then be reduced gradually to a maintenance dose. BTS recommendations do not advise inhaled steroids as initial or maintenance treatment, but suggest they may have a place in managing selected patients to control cough. With regard to monitoring for adverse effects, potentially serious side-effects are well recognized and the principles used in other clinical settings generally apply.
National evidence-based guidelines for the prevention of steroid-induced osteoporosis provide valuable advice. Physicians may however wish to avoid prescribing calcium and vitamin D supplements in patients with sarcoidosis unless they also monitor serum and urine calcium levels. The dose of calcium and vitamin D can then be tailored according to these parameters. With bisphosphonates, clinicians should be aware of the risk of osteonecrosis of the mandible and be ready to advise patients to have an initial dental examination and appropriate preventive dentistry.
When treating females of child-bearing age, they should also be aware that these agents are not recommended in pregnancy. Current British ILD guidelines recommend considering other immunosuppressive agents when corticosteroids are not controlling the disease, or when side-effects are unacceptable, with methotrexate the agent of choice. Lung transplantation should be considered in end-stage pulmonary sarcoidosis. Sarcoidosis is the commonest ILD and is often managed by respiratory specialists. Despite experience of over 50 years using oral corticosteroids, their long-term benefits remain unclear, as is the value of inhaled corticosteroids.
General management strategies include clear patient information and smoking cessation advice. Pulmonary rehabilitation, oxygen supplementation and palliative care may be appropriate in patients with severe pulmonary fibrosis. There is broad agreement on the initial dose, subsequent tapering and length of treatment.