An Overview of Respiratory Disease in Pregnancy

Dr Ben Sutton Respiratory Physician Queen Elizabeth Hospital Birmingham

Evolution of the female respiratory centre

Research Open Access Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease Tarja Saaresranta*1,2, Tero Aittokallio3, Karri Utriainen1 and Olli Polo1,2,4

Premenopausal women Experience significantly less sleep disordered breathing HRT reduces OSA by 50% in Post menopausal women

Hyperventilation Drives Protective Maternal/Foetal Acid Base Changes

Progestogens Hyperventilation Reduced pCO2 Increased pO2 Reduced HCO3 pH at alkalotic end of normal

Maternal

Protects against acidosis Increases paO2 Drives left shift of Hb F

8-10kPa gradient

Healthy Babies

Lung function In Pregnancy

BG Cooper Thorax 2010

In a normal pregnant female lung function is unaffected by pregnancy Ventilation is maintained by a reduction in Functional Residual Volume In patients who already have abnormal spirometry expect further 10-15 % reduction in FVC

Summary of respiratory changes in pregnancy

• Breathlessness is normal

• Borderline Respiratory alkalosis is physiologically normal and reduces foetal mortality

• Pregnancy doesn’t reduce PFT’s unless pre-existing lung disease –then may reduce by 10-15%

Progesterone induces hyperventilation

40% increase In cardiac Output and circulating volume

D

Comp resp alkalosis Low CO2 Low HCO3 Normal paO2

Anaemiai

Diagnosis and Management of VTE

Background

41 deaths in 2003-2005 reduced to 18 deaths 2006-2008 1

Risk of VTE in pregnancy approximately 5 x age matched controls but absolute risk is low – less than 1 in 1000 pregnancies

Greatest risk is puerperium* – estimates up to 20 fold increase

1 MBRRACE-UK 2015 *Puerperium = delivery to normalisation of maternal reproductive organs – 6 weeks

What is the Clinical Utility of pre investigation assessment??

Subjective clinical assessment in VTE is generally poor – 50/50 Subjective clinical assessment in pregnancy is also unreliable Studies suggest 2-6% of suspected PE’s ultimately confirmed by objective investigation

Take home message

• There is no validated role for our usual approach to excluding VTE in pregnancy

• All suspected VTE should be treated and actively excluded with objective investigation

Risks of V/Q vs CTPA

CTPA V/Q

Subsequent Childhood malignancy

1 in 280 0001 risk of neonatal thyroiditis from IV contrast

1 in 100 000

Maternal Breast Cancer 1 in 5000 additional risk 3 1 in 170 000

Diagnostic Utility 0.4% chance of PE in 3/12 with technically adequate scan2 99.6% PPV

High probability scan 1% risk of PE in 3 months but up to 21% risk of intermediate probability scan 8% risk of PE at 3/12 low probability scan

1- BTS guideline, 2 - BMJ 2005; 330; 3- Law J, Faulkner K Cancers detected and induced, and associated risk and benefits, in a breast cancer screening programme. Br J Radiol 2001

Take home message

• The absolute risk to mother and child is low regardless of modality and investigation should not be deferred due to this

• CTPA has negligible risk to child but potential increased risk to mother

• Good quality V/Q is almost as good as CTPA but significant risk of suboptimal scan and 8% risk of PE with a low risk scan

• The highest period of radiation exposure risk is at peurperium where both tests are essentially equal

Respiratory Tract Infection In Pregnancy

“Pregnancy is natures most successful allograft”

Lancet 2009;375:1417

Balance in Th1 Th2 immunity

2009 flu pandemic- risk of development of flu during pregnancy

Incidence, Mortality and morbidity of Pneumonia in pregnancy

Background rate in adults 19-59yrs 5-8/1000 Risk highest between 24-31 weeks Asthma increases risk by 5 fold

Antepartum steroids for lung maturity increase risk (64% v 17.5%)2

1Thorax 2001;56:398-405 2;AsthMunn MB, Groome LJ, Atterbury JL, et al. Pneumonia as a complication of pregnancy. J Matern Fetal Med 8:151–154, ma increases risk by 5 fold

Foetal outcome in Mothers with Pneumonia

• Significant increase in chance of delivery before 34 weeks and preterm delivery in 43%1

• Average reduction birthweight of 150g

• Frequency of babies below 2500g 16% vs 8% in controls 2

2 Yost NP, Bloom SL, Richey SD, et al. (2000) An appraisal of treatment guidelines for antepartum community-acquired pneumonia. Am J Obstet Gynecol

1 Munn MB, Groome LJ, Atterbury JL, et al. (1999) Pneumonia as a complication of pregnancy. J Matern Fetal Med 8:151–154,

Antimicrobials in pregnancy

Thorax 2001;56:398-405 doi:10.1136/thorax.56.5.398

Take home messages

• Pregnancy is an immunosuppressive state

• The incidence and maternal mortality of bacterial CAP is similar to the non pregnant female population but pregnant women with CAP are more likely to have premature or small birthweight babies

• Treat aggressively-routine antibiotics are safe

• Pregnant women are more susceptible to Influenza A due to reduction in TH1/NK cells

• Influenza in pregnancy is associated with severe disease and increased risk of complications to mother and baby

• Pregnant women with febrile respiratory tract illness should be screened and treated for Influenza if seen on take

• All pregnant women should be encouraged to be vaccinated against influenza regardless of trimester

Background • Asthma is the commonest chronic disease in pregnancy –

up to 1/8

• Still a rule of thirds

• Worsens at start of second trimester and peaks at 6 months

• Honeymoon period from 36 weeks when symptoms improve

• 90% of women have a normal birth with no step up in therapy

• Prior pregnancies usually predict subsequent pregnancies

Complications of poor asthma control in pregnancy

• Hyperemesis

• Hypertension

• Pre-eclampsia

• Vaginal Haemorrhage

• Growth Restriction and low birth weight

• Neonatal Hypoxia

• Increased risk of gestational diabetes

• OR 1.4 of caesarean section but ? Due to pre-planning

TH2 pathways in Asthma

iNOS

eNO Extrinsic/ classic asthma

Intrinsic non atopic

Pregnancy

Haldar et al 2007

Rule of thirds in pregnancy – Th1 response is reduced Th2 is exacerbated

Th1/Non Th2

Th2

Risk of Exacerbation and requirement for hospitalisation vs severity of

asthma 52% risk

27% admission

26% risk of exacerbation 7% risk of admission

13% exacerbation 2%risk of admission

BTS/SIGN British Guideline on he management of asthma 2014

Drug Safety in Asthma Drug Safety data

evidence Risk Advice Possible

complications

SABA High None known Use normally Usual s/e

LABA High None known Use normally Usual s/e

Inhaled Corticosteroids

High Low Use normally Infection risk

Leukotrienes Low to moderate

Unknown- manufacturer stop

Assess risk vs benefit

Foetal loss 1st Trimester

Oral steroids High Low to moderate

Use Risk v benefit

Infection, C pal Gest Diabetes

Theophyllines High None known Use Check levels

Magnesium So4

High None known Use Usual s/e

Aspirin High Moderate Risk V benefit Exac of asthma

Prostaglandins Theoretical High Caution Severe B spasm

Anti Ig E None Unknown Review in BRSAS MDT

Unknown

Adapted from BTS Asthma Guidelines

Breast Feeding in asthma is safe

• Breast feeding reduces risk of asthma for mother and child

• <1% theophylines recovered in breast milk 1

• Prednisolone level in breast milk is 5-25% of serum level = 0.1% of original oral/IV dose 2

Ost et al Prednisolone excretion in human milk Br J Paed;1985:106:1008-11 Turner ES Management of the pregnant asthmatic patient Ann Inter Med 1980 93(6):905-18

Risk vs Benefit is relative

• 32 y.o female atopic asthma – 8 weeks into trial of anti Ig E therapy

• Becomes G2 P1 (supposed to be on OCP)

• Last pregnancy required 40mg maintenance prednisolone

• 3 admissions including HDU stay

• First child born at 32 weeks, small for dates

• After MDT discussion 3 x respiratory consultants and immunologists patient offered continuation of therapy

• Delivers at 38 weeks with one exacerbation and no admissions, average prednisolone 20mg

• Child fails to thrive and is found to have severe nephrotic syndrome requiring sequential nephrectomy

• Subsequently proven to be independent genetic abnormality- nephrin – relief all round

Take home messages

• Poorly controlled asthma is associated with increased risk for mother and child

• Acute asthma should be treated aggressively with all usual medications

• Drugs are safe and compliance should be strongly promoted with close monitoring

• Although some asthma may worsen safe delivery and healthy child should be normal with good asthma control

Complex Respiratory Disease

• 30 yr old lady – G1 P0 with fibrous ostiotic dysplasia – McCune Albright Syndrome

• Presents as emergency to BWH 28+1 with respiratory distress

• Wheezy but also features of fluid overload

• Ph 7.37, O2 7.7, Co2 5.2

• Blood eos 0.9, CRP neut normal

• No History of asthma

• Multiple orthopaedic procedures on both hips pelvis and femurs

• Facial corrective surgery

• GTT at 20/40 and endocrine review- normal

• Seen by cardiology – heart failure and given diuretics with good effect – 1.5L diuresis – echo poor views

• Also treated with nebs and high flow oxygen

• Asked to review

Baseline CXR

Lung function

Overnight sleep studies

• Investigations suggest combination of pregnancy related asthma with severe restrictive lung disease and presumed right heart failure

• ICS/LABA, salb nebs qds and prednisolone to be weaned to 15 mg

• Ph 7.44, co2 4.1, po2 >10

• 31+5, aim to deliver at 37/40 with review at 34 weeks

Questions ?