Early encouraging reports of mist tent therapy (Matthews LW et al. Pediatrics 1967; 39:176 below; Doershuk CF et al. Pediatrics 1968; 41:723; Parks CR. J Pediatr 1970; 76: 305) were eventually followed by others failing to demonstrate benefit from the treatment (Motoyama EK et al. Pediatrics 1972; 50:299 below; Chang N et al. Am Rev Respir Dis 1973; 107:672 below) and the mist tent treatment was eventually abandoned by most, but not all clinics, in the early Seventies.

A small child with CF in a mist tent, 1963, from Louis Schwab, Cornelia B. Callison, and Marilyn Pierce Frank, “Cystic Fibrosis,” The American Journal of Nursing 63, no. 2 (1963).

1951 Denton R, Smith RM. Portable humidifying unit. II. Large capacity metal nebulizer. Am J Dis Child 1951; 82:433- 438. [PubMed]
Robert Denton of Philadelphia was a scientist whose wife, Wynne Sharples, was a paediatrician – they had two children with cystic fibrosis. This is one of Robert Denton’s early papers which was said to set the scene for mist tent therapy. Soon Denton produced a clinical paper describing mist tent therapy (Denton R. Dis Chest 1955; 28:123-140 below) which was eventually widely used in the USA.

1955 Denton R. The clinical use of continuous nebulization in bronchopulmonary disease. Dis Chest 1955; 28:123-140. [PubMed]
Robert Denton, a scientist, and his wife Wynne Sharples, a paediatrician, observed that their two children with CF appeared to improve when they slept in tents into which was nebulised 3% saline or a dilute 10% propylene glycol solution. However, although the concept of continuous nebulisation was described as a new technique, its use in CF was not mentioned in this particular paper.
Harry Shwachman also used mist tents from 1958 and initially was impressed by their effectiveness in patients with CF who had thick bronchial secretions. The experience of authorities such as Leroy Matthews, Robert Denton and Harry Shwachman led to the incorporation of mist tent therapy into CF treatment programmes including the Cleveland Comprehensive Treatment Programme (Matthews et al, 1964 below). Eventually the mist tent was recommended by the US CF Foundation (figure above) through the Sixties until a number of studies failed to confirm the impression that the treatment was of benefit.

Shwachman (somewhat changing his ground!) later recalled that “a group of doctors in Cleveland (Matthews et al, 1964) started using the mist tent. Because they were enthusiastic over it and thought it was good we tried it. But after 5 or 6 years we asked our parents if they noticed any improvement and they said no. We tried it on and off and decided it didn’t help”.

Although mist tents were widely used in North America for people with CF they were never popular in the UK and eventually their use was abandoned after trials in the late Sixties failed to show significant deposition of fluid in the lower airways or clinical benefit.

Robert Denton published nearly 40 papers mostly on mechanical factors in airway secretion from the early Fifties including nebulisation, effects of mechanical percussion, rheology of sputum and the mucolytic acetyl cysteine. His wife Wynne Sharples was also involved with the CF Foundation in the early years.

1967 Matthews LW, Doershuk CF, Spector S. Mist tent therapy of obstructive pulmonary lesion of cystic fibrosis. Pediatrics 1967; 39:176-185. [PubMed]
This paper from Cleveland, from one of the most respected clinical groups in the USA, was considered to provide evidence of the efficacy of mist tent treatment which was by this time widely used in the USA. After three control periods the addition of mist tent therapy to an otherwise comprehensive treatment programme resulted, over the next two months, in significant decrease in functional residual capacity, residual volume and ratio of residual volume to total lung capacity – changes that were maintained over the next year.

In commenting favourably on this paper at the time Paul di Sant’Agnese implied that clinicians with experience of treating people with CF would agree with the authors’ findings and stated – “the results reported here confirm the clinical observation of the value of mist tent therapy…it is generally accepted by almost all clinicians, who have had adequate experience with this disease, that most patients have considerable benefit from such a treatment programme”. Di Sant’Agnese continued “we must conclude from all available clinical, physiologic and pathologic evidence that, in addition to the judicious use of antibiotic agents, all types of inhalation and physical therapy should be used in therapy of pulmonary involvement of cystic fibrosis”.
Despite this support from leading CF clinicians of the time, the treatment was later discredited and gradually abandoned by most of them in the early Seventies (See also Doershuk et al, 1968 below). Mist tent therapy was never popular in the UK. But perhaps the possible benefits of nocturnal humidification will be re-examined in the light of the low salt theory of pathogenesis of the respiratory problems?

1967 Avery ME, Galina M, Nachman R. Mist Therapy. Pediatrics 1967; 39:160-165. [PubMed]
In the same issue of Pediatrics as Matthews et al, 1967 (above) paper on mist tent therapy, Mary Ellen Avery wrote a detailed critical review of mist therapy and concluded – “At present the technical advances in the generation of mists and knowledge of the deposition of particles exceeds knowledge of the role of mists in the treatment of respiratory disorders. Some evidence exists that viscous secretions can be thinned by mist; upper airway cooling and drying can be decreased by added humidity. So the doubts about mist therapy were beginning to be expressed.

Mary Ellen Avery was Professor of Pediatrics at Harvard and the first woman-in-chief at the Children’s Hospital, Boston.

1968 Doershuk CF, Matthews LW, Gillespie CT, Lough MD, Spector S. Evaluation of jet-type and ultrasonic nebulizers in mist tent therapy for cystic fibrosis. Pediatrics NY 1968; 41:723-732. [PubMed]
Mist tents were still a very popular form of treatment in the USA in the late Sixties particularly in the Cleveland clinic. Ultrasonic nebulisers were said to be better then jet nebulisers for mist tent therapy. However, towards the end of the decade the use of mist tents was increasingly questioned until eventually a number of studies failed to show benefit from the overnight treatment (Bau et al, 1971 below; Norman & Hall Practitioner, 1971; 206: 786-789 below; Motoyama et al, Pediatrics 1972; 50:299; Chang et al, Am Rev Resp Dis 1973; 107:672 below). Certainly the Mistogen compressor nebuliser system gave a very fine dense mist into the tent.

1969 Lawson D. Discussion on the therapeutic and prophylactic use of mist tents. Proc 5th Int CF Conference, Cambridge, 1969. Ed. Lawson D. London. Cystic Fibrosis Research Trust 1969:149-168.[Conference]
Opinions of many of the leading authorities of the time were divided but all agreed there was a need for clinical trials. The Europeans and North Americans were in favour of mist tents but UK were not. The discussion seemed to move towards nebulised antibiotics; Leroy Matthews was enthusiastic about nebulised gentamicin later used with carbenicillin by Margaret Hodson (Hodson et al, 1981 below).

1969 Anonymous. Inhalation and mist tents in cystic fibrosis. Lancet 1969; 2(7626):891-892. [PubMed]
A review of the increasing doubts regarding the use of mist tent therapy noting that most of the liquid was deposited in the upper respiratory tract – although breathing through a wide bore tube was more effective. Although Leroy Matthews is mentioned as producing evidence of a beneficial effect (Matthews et al, 1967 above) it was suggested that trial should be given to all sorts of inhalation therapy for the individual patient, either intermittent aerosols or mist tents. A controlled trial seemed to be indicated.

1970 Mearns MB. Aerosol therapy in cystic fibrosis. Arch Dis Child 1970; 45:605-607[PubMed]
Margaret Mearns from the UK reviewed the situation regarding the somewhat controversial nocturnal mist tent therapy which was at this stage recommended by the US CF Foundation with strong support from Leroy Matthews and his colleagues at the Cleveland clinic. Mearns notes that Doershuk et al, 1964 and Matthews et al, 1967 from Cleveland showed improvements in respiratory function after nocturnal mist therapy which regressed when the treatment was withdrawn. Doershuk et al, (Pediatrics 1968; 41: 723) reported good results in more severely affected children using ultrasonic nebulisers however, Matthews et al, (J Asthma Res 1968; 5:267) reported subsequent deterioration of the earlier reported patients at 24 months although they had been improved at 12 months. Mearns mentions that Norman et al, 1969 in London showed no benefit from 2 years of nocturnal mist therapy. Finally Matthews et al, in 1969 (5th International CF Conference Cambridge, 1969:155) found a trend towards normal in early cases considering only 10% showed evidence of progressive lung damage over an average of seven years.

Margaret Mearns noted the need for a well-controlled trial and that “at this stage sitting on the fence is rarely a commendable or comfortable posture and it is one adopted only with reluctant necessity by the present writer after appraisal of the available facts about mist therapy”.

Subsequently a number of studies confirmed the doubts many clinicians had regarding nocturnal mist therapy (Bau et al, 1971 below; Chang et al, 1973 below) and their use diminished during the Seventies.

The mist tent story would have raised an “I told you so” from enthusiasts of Cochrane Systematic Reviews in that a demanding, time-consuming, involved treatment had been introduced and officially recommended – even supported by such experts as Shwachman and di Sant’Agnese – before any controlled trial. Yet when it was put to the test of a controlled trial, failed to showed significant benefit. However, nothing is entirely straightforward, as Robert Wood in a detailed review of the treatment in 1976 did not condemn mist tent therapy out of hand (Wood 1976 below). One wonders if another look at mist therapy would be in order in 2012 in view of the current support for the low salt theory of pathogenesis and the improved nebulisation possibilities?

1971 Bau SK, Aspin N, Wood DE, Levison H. The measurement of fluid deposition in humans following mist tent therapy. Pediatrics 1971; 48:605 – 612. [PubMed]
Mist from an ultrasonic nebuliser labelled with technetium 99m was inhaled in mist tents for an hour by six control patients and eight patients with cystic fibrosis. No attempt was made to control the rate or depth of breathing nor to encourage mouth or nasal breathing. Less than 5% of the radioactivity nebulised and distributed in the tent entered the body – of this 90% lodged in the nasopharynx, was swallowed and rapidly appeared in the stomach. Very little activity was detected over the lungs. The authors concluded – “If mist tents are of value in the treatment of cystic fibrosis the benefit must accrue from reasons other than the deposition of significant quantities of fluid in the lung”.

This was one of a number of studies which cast increasing doubts on the value of nocturnal mist therapy. Henry Levison’s group in Toronto went on to do a small clinical trial which failed to show benefit from nocturnal mist therapy (Chang et al, 1973 below). As mentioned above, Robert Wood questioned the accuracy of the labelled technetium studies as apparently the isotope is removed very rapidly from the airways – also he had observed considerable fluid deposition in the airways when performing bronchoscopies soon after mist tent therapy (Wood et al. 1976, below).

1971 Norman AP, Hall M. Nocturnal mist therapy in cystic fibrosis. Practitioner 1971; 206:786 -790[PubMed]
Archie Norman was unable to show any difference in any objective findings of respiratory or nutritional state between 10 treated in mist tents at night and 10 control children with CF over two years. He commented on the many practical difficulties of delivering the treatment and maintaining the equipment. Only one of nine treated families opted to continue with the tent after the trial ended – this is probably significant indicating the parents had not observed any benefit.

1972 Motoyama EK, Gibson LE, Zigas CJ. Evaluation of mist tent therapy in cystic fibrosis using maximum expiratory flow volume curves. Pediatrics 1972; 50:299 – 306. [PubMed]
Sixteen patients with CF were studied every two weeks over four to five months. Half had an initial eight to 12 weeks off mist therapy; the other half had conditions reversed. No improvement occurred with mist tent therapy – in fact, a small decline occurred. Bacterial contamination was present in two thirds of the tents.

So here was further evidence against the use of mist tents (also Norman et al, 1971; Bau et al, 1971; Chang et al, 1973; Bureau et al, 1978).

1973 Chang N, Levison H, Cunningham K, Crozier DN, Grosett O. An evaluation of nightly mist tent therapy for patients with cystic fibrosis. Am Rev Resp Dis 1973; 107:672-675. [PubMed]
One of the main studies that led to the abandonment of nocturnal mist therapy. The study was from Henry Levison’s department in the Toronto clinic on 26 patients with CF into the effects of mist tent therapy by assessing changes in clinical condition, pulmonary function and blood gas tensions with and without mist tent therapy for a total period of 6 months. The authors concluded that “The nightly mist tent therapy had no beneficial effect in patients with cystic fibrosis. The severity of the pulmonary disease and the type of nebuliser had no apparent effect on the results”. However, a subjective analysis by patients and parents had eight feeling “better”, four “worse” and 14 noticed “no difference”.

At this time nightly mist tents were the recommended treatment in the National Cystic Fibrosis Research Foundation’s Guide to Diagnosis and Management of Cystic Fibrosis. 1971. This study by Chang et al. was rather short term and entirely concerned with respiratory function tests, in fact, subjectively no less than 30% of the patients felt better in the tent! Also the use of nightly mist tents was supported by many leading CF clinicians in the USA including Paul di Sant’Agnese, Harry Shwachman, Carl Doershuk and Leroy Matthews. (See also Bureau MA et al, Pediatrics 1978; 61:842-846.[PubMed]for more prolonged study of mist tent use. Also discussion after Wood 1976 below)

1976 Wood RE, Boat TF, Doershuk CF. State of the Art. Cystic Fibrosis. Am Rev Respir Dis 1976; 113:833-878. [PubMed]
Dr Robert Woods provides an excellent very detailed review (with 500 references) of the CF situation in 1976 in the USA when the 50% survival there was 15 years. The discussion of mist tent therapy, which was falling out of favour at the time, was particularly interesting. Woods mentions that early studies were encouraging (Doershuk et al, 1968 above; Matthews et al, 1967 above) but later studies had not shown a beneficial response (Motoyama et al, 1972 above; Chang et al, 1973 above). However, although studies of radioactive aerosols showed little radioactivity in the lungs (Wolsdorf J et al. Pediatrics 1969; 43:799; Bau SK, et al. Pediatrics 1971; 48:605). Woods suggests that significant deposition may have been masked by the rapid absorption of the radioactive aerosol which was known to occur. He questioned the techniques used in some of the aerosol studies and noted that, at bronchoscopy, he had observed large amounts of mist particles reaching at least the subsegmental bronchi even during nasal breathing. In fact he considers it possible that the radioactivity at any particular site may bare little relation to the amount of fluid deposited.

The implication of these observations was that the final word had not been said on mist tent therapy. This is all particularly relevant now in view of the present belief that the low salt theory and drying of the epithelial surfaces accounts for the increased viscosity and easy tendency to infection within the airways. It is worth recalling that highly experienced clinicians such as Shwachman, di Sant’Agnese and particularly Leroy Matthews all were impressed by the benefits of mist tent therapy as were some patients who took part in the Toronto studies (Chang et al. 1973).

1978 Bureau MA, McDougall DM, Beaudry PH, Belmonte MM. Late effects of nocturnal mist tent therapy related to the severity of airway obstruction in children with cystic fibrosis. Pediatrics 1978; 61:842-846. [PubMed]
A study from Montreal to evaluate the long-term effect of nocturnal mist tent therapy on the progression of airway obstruction in children with CF of varying severity. Two matched groups each consisting of 24 children with CF were studied during 18 months on mist tent therapy and 18 months off therapy. The mist therapy failed to benefit any of the groups of children with CF who had early, moderate, or advanced airway obstruction as judged from their respiratory function tests (MMEF values).

The authors concluded that nocturnal mist tent therapy neither decreases airway obstruction nor prevents its progression in children with cystic fibrosis. The authors mention their findings are similar to those of Jehanne M et al, Ann Pediatr 1974; 21:595 extending for up to 2 years. Other studies failed to confirm benefit from nocturnal mist tent therapy (Bay et al. 1971; Norman & Hall. 1971; Moyatama et al, 1972; Chang et al 1973 – all above).

2000 Jakobsson B. Hjelte L. Nyström B. Low level of bacterial contamination of mist tents used in home treatment of cystic fibrosis patients. J Hosp Infect 2000; 44:37-41. [PubMed]
Mist tents are recommended by the Stockholm cystic fibrosis (CF) centre for small children with CF. The disinfection procedures recommended are reviewed – including by home visits. No or insignificant growth was found in 16/20 aerosol tubes: moulds in three, Pseudomonas species in one. Twelve of 19 chambers showed no or insignificant growth: moulds or yeasts were present in three and Pseudomonas sp. in four. In four of the seven patients moulds or yeasts and/or Pseudomonas sp. grew both from chambers and from aerosol tubes; in the remaining three only from chambers. None of these seven patients had followed our prescribed cleaning and disinfection recommendations. The authors conclude that our disinfection recommendations are adequate when followed. The different forms of non-compliance would not have been detected without a home visit, emphasizing the importance of such visits. The importance of drying the equipment and of using the correct concentration of acetic acid is stressed.

–   It is interesting that mist tents are still only used in Stockholm. When in widespread use it was always a concern that they may be a source of infection if not meticulously cleaned. Before dismissing the use of mist tents it is worth considering the increasing support for the importance of the fluid layer of the respiratory epithelium and also Robert Woods (1976 above [PubMed]) comments that he had observed considerable moisture in the airways when bronchoscoping patients after mist tent therapy!

Labonte ML.The Mist Tent: An Analysis of Therapeutic Change in the History of Cystic Fibrosis Care.
Bull Hist Med.
 2018;92(4):634-663. doi: 10.1353/bhm.2018.0074. [PubMed]

Michelle Lynne Labonte

Mist tent therapy for cystic fibrosis went through a rise and fall in popularity between the 1950s and 1970s, providing an opportunity to explore the nature of therapeutic change in medicine. The therapy “worked” in the context of a particularly grim life expectancy in the early 1950s and in the setting of a comprehensive therapeutic program that began in Cleveland in 1957. Although clinical studies published in the 1970s provided evidence that mist tents were ineffective or even harmful, these later studies were not necessarily more robust than earlier studies that provided evidence of mist tent efficacy, suggesting that other factors may have also contributed to mist tent abandonment. In fact, the unpalatable nature of mist tent therapy, which was described by one doctor as akin to incarceration, and studies that questioned the theoretical underpinnings of the therapy also played important roles in the eventual abandonment of misttents.

– As noted above before dismissing the use of mist tents it is worth considering the increasing support for the importance of the fluid layer of the respiratory epithelium and also Robert Woods (1976 above [PubMed]) comments that he had observed considerable moisture in the airways when bronchoscoping patients after mist tent therapy! This article provides a very detailed and readable account of mist tent therapy in CF patients over the years.